Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lyci...Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.展开更多
The expression and clinical significance of relevant cytokines in otitis media (OM) are discussed, and the alterations to the pathological state of the otitis media mucosa are further understood through the study of c...The expression and clinical significance of relevant cytokines in otitis media (OM) are discussed, and the alterations to the pathological state of the otitis media mucosa are further understood through the study of cytokine transduction pathways. More and more studies have shown that relevant cell proliferation and inflammation progression pathways play a role in the development of otitis media, such as the Jun amino-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway, the NF-κB signaling pathway, and the PI3K/AKT/PTEN pathway, which are involved in the proliferation of the middle ear mucosa during otitis media, which affects the mucosal cilia, motor function, Eustachian tube function, and the mucosal ciliary function. These studies provide new ideas for the treatment of otitis media and further explore the feasibility of immunotherapy in the future treatment of otitis media. In this paper, we present a review of the latest research progress on the expression of various cytokines in otitis media.展开更多
BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a c...BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.展开更多
Background:Acne vulgaris(AV)is a common inflammatory skin disease.Although various mechanisms have been indicated in the etiopathogenesis of AV,the exact pathophysiology remains unknown.Various lasers have been used t...Background:Acne vulgaris(AV)is a common inflammatory skin disease.Although various mechanisms have been indicated in the etiopathogenesis of AV,the exact pathophysiology remains unknown.Various lasers have been used to treat AV;however,the serum level changes of inflammatory cytokines after laser therapy have not been elucidated.We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595-and 1064-nm dualwavelength laser.Methods:In total,18 patients(9 male and 9 female)between 16 and 35 years of age with moderate to severe AV were evaluated in the study.Disease severity was classified according to the Pillsbury grading system of acne.Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment.A 3 mL blood sample was drawn from every subject each time,and serum levels of inflammatory cytokines such as interleukin(IL)-6,IL-8,and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment.Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation.Results:Inflammation was significantly reduced on both the treated and untreated sides,and symptoms of AV lesions were alleviated.All patients showed a significant increase in serum IL-22 levels after the first laser therapy,with no significant difference in serum IL-6 and IL-8 levels.After the second laser therapy,serum IL-6,IL-8,and IL-22 levels were significantly decreased.No significant side effects such as bruising,edema,hyperpigmentation,hypopigmentation,or scarring were reported.Conclusion:Half-face treatment with 595-and 1064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission,which was associated with a gradual decrease in IL-6,IL-8,and IL-22 levels after half-face topical treatment.This suggests that reducing inflammatory cytokine levels in the serum can relieve inflammation in non-therapeutic sites.This laser treatment is effective,economical,and painless.展开更多
The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully d...The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled.To control cognitive function and behavior,the two systems are engaged in a subtle interacting act.In this scenario,a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging.Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes.In this dynamic equilibrium,synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro-and anti-inflammatory molecules in the central nervous system microenvironment.展开更多
Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating a...Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.展开更多
Myelomeningocele(MMC)is a severe form of spinal dysraphism.Due to the failure of neural tube closure during early embryonic development,the affected part of the spinal cord is left open like a book at the back of the ...Myelomeningocele(MMC)is a severe form of spinal dysraphism.Due to the failure of neural tube closure during early embryonic development,the affected part of the spinal cord is left open like a book at the back of the affected child.This malformed part of the spinal cord is not covered by its protective mesodermal and ectodermal derived layers.Consequently,the exposed neural tissue(i.e.,the neural placode)is prone to injuryduring further intra-uterine development.展开更多
Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United...Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.展开更多
Objective:To explore the effect of"Yingxiang-Hegu"on Th1,Th2-related cytokines and[2]transcription factors T-bet and GATA-3 in rats with allergic rhinitis.Methods:Rats were randomly divided into three groups...Objective:To explore the effect of"Yingxiang-Hegu"on Th1,Th2-related cytokines and[2]transcription factors T-bet and GATA-3 in rats with allergic rhinitis.Methods:Rats were randomly divided into three groups:blank group,model group and acupoint group.The rat model of ovalbumin(OVA)AR was established,and the general condition of the rats was observed and scored.Acupuncture intervention was performed on the acupoint group on the second day after successful modeling,once per day for 20 min for 10 d.After intervention,the general behavior,behavioral score and histomorphological changes of nasal mucosa were observed.Eosinophils(EOS)were counted under microscope after nasal lavage smear staining,and the contents of total IgE,IFN-γ,IL-12,IL-4 and IL-5 in serum were detected by ELISA.Westernblot and IHC were used to detect the protein level and positive protein expression of specific transcription factors T-bet and GATA-3 in rat nasal mucosa.Results:After the establishment of the model,except for the blank group,the behavioral observation scores of rats in the model group and acupoint group were more than 5 points,indicating that the model was successful.After acupuncture intervention on acupoint"Yingxiang-Hegu",the behavioral score of rats in the acupoint group and western medicine group was significantly lower than that in the model group(P<0.05).Microscopic examination showed that the structure of nasal mucosa in the model group was obviously damaged,cilia were arranged discontinuously,uneven,local congestion and swelling,a large number of epithelial cells exfoliated and necrotic,goblet cell proliferation,obvious inflammatory cell infiltration.The pathological degree of nasal mucosa in the pair point group was significantly less than that in the model group.Compared with the model group,the levels of IFN-γ,IL-2 and IL-12 in serum were significantly increased,while IgE,IL-4,IL-5 and IL-6 were significantly decreased,GATA-3 protein and positive expression in nasal mucosa were significantly decreased and T-bet was significantly increased after acupuncture.Conclusion:Acupuncture at"Yingxiang-Hegu"can effectively improve the nasal sensitive symptoms and control nasal inflammation in AR rats.The mechanism may be that acupuncture at Yingxiang-Hegu can up-regulate the expression of T-bet,decrease the level of GATA-3,promote the production of Th1 cytokines and inhibit the synthesis and secretion of Th2 cells,thus restoring the immune balance of Th1 and Th2.展开更多
Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 na...Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 nasopharyngeal carcinoma patients with oral mucositis after intensity-modulated radiation therapy(IMRT)were randomly divided into the control group(CG)and the observation group(OG),with 42 cases in each group.The CG was given LLLT,and the OG was treated with Kangfuxin Solution in addition to LLLT for 10 consecutive days.The healing time of oral mucosa,mucositis grading,oral pain scores,cytokines(interleukin-6,interleukin-1βand tumor necrosis factor-α)and T lymphocyte subsets were compared between the 2 groups before and after treatment.Results:The healing time of oral mucosa in the OG was(6.8±1.4)d,which was significantly shorter than(8.6±1.9)d in the CG(t=4.943,P<0.01).After treatment,the grading of oral mucositis in the OG was better than that in the CG,with a statistically significant difference(Z=2.942,P<0.05).The oral pain scores of the OG was lower than that in the CG at different time points after treatment,and the difference was statistically significant(t=8.207,11.017,P<0.01).After treatment,the levels of IL-6,IL-1βand TNF-αin peripheral blood of the OG were significantly lower than those in the CG(t=5.217,2.775,4.053,P<0.01).There were statistically significant differences in CD4+,CD8+and CD4+/CD8+between the OG and the CG after treatment(t=5.692,6.093,3.658,P<0.01).Conclusion:Kangfuxin Solution combined with LLLT can significantly shorten the healing time of oral mucosal,reduce the grading of oral mucositis,relieve oral pain,reduce inflammatory response and improve the immune function of patients.展开更多
AIM To observe the effect of acupuncture and moxibustion on the expression of IL 1β and IL 6 mRNA in ulcerative colitis rats. METHODS The SD rat ulcerative colitis model was created by immunological method associated...AIM To observe the effect of acupuncture and moxibustion on the expression of IL 1β and IL 6 mRNA in ulcerative colitis rats. METHODS The SD rat ulcerative colitis model was created by immunological method associated with local stimulation. Colonic mucosa was prepared from human fresh surgical colonic specimens, homogenized by adding appropriate amount of normal saline and centrifuged at 3000*!r/*!min . The supernatant was collected for measurement of protein conentration and then mixed with Freund adjuvant. This antigen fluid was first injected into the plantae of the model group rats, and then into their plantae, dorsa, inguina and abdominal cavities (no Freund adjuvant for the last injection) again on the 10th, 17th, 24th and 31st day. When a certain titer of serum anti colonic antibody was reached, 2% formalin and antigen fluid (no Freund adjuvant) were administered separately by enema. The ulcerative colitis rat model was thus set up. The animals were randomly divided into four groups: model control group (MC, n =8), electro acupuncture group (EA, n =8), herbs partition moxibustion group (HPM 8), normal control group (NC, n =8). HPM: Moxa cones made of refined mugwort floss were placed on the medicinal pad (medicinal pad dispensing: Radix Aconiti praeparata, cortex Cinnamomi, etc ) for Qihai (RN 6) and Tianshu (ST 25, bilateral) and ignited. Two moxa cones were used for each acupoint once a day and 14 times in all. EA: Tianshu (bilateral) and Qihai were stimulated by the intermittent pulse with 2Hz frequency, 4mA intensity for 20 minutes once a day and 14 times in all. After treatment, rats of all four groups were killed simultaneously. The spleen was separated and the distal colon was dissected. Total tissue RNA was isolated by the guanidinium thiocyanate phenol chloroform extraction method. RT PCR technique was used to study the expression of IL 1β and IL 6 mRNA. RESULTS IL 1β and IL 6 mRNAs were not detected in the spleen and colonic mucosa of the NC rats, whereas they were significantly expressed in that of the MC rats. IL 1β and IL 6 mRNAs were markedly lower in the EA and HPM rats than that in MC rats. There was no significant difference between the levels of IL 1β and IL 6 mRNAs in the EA and HPM rats. The expressions of IL 1β and IL 6 mRNAs were nearly the same in the spleen and colon of all groups. CONCLUSION Acupuncture and moxibustion greatly inhibited the expression of IL 1β and IL 6 mRNA in the experimental ulcerative colitis rats.展开更多
Nonalcoholic fatty liver disease(NAFLD)is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis.The pathogenesis of NAFL...Nonalcoholic fatty liver disease(NAFLD)is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis.The pathogenesis of NAFLD and nonalcoholic steatohepatitis(NASH)has not been fully elucidated.The"two-hit"hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH.It should be better regarded as a multiple step process,with accumulation of liver fat being the first step,followed by the development of necroinflammation and fibrosis.Adipose tissue,which has emerged as anendocrine organ with a key role in energy homeostasis,is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins.These adipocyte-specific or enriched proteins,termed adipokines,have been shown to have a variety of local,peripheral,and central effects.In the current review,we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD.We particularly focus on adiponectin,leptin and ghrelin,with a brief mention of resistin,visfatin and retinol-binding protein 4 among adipokines,and tumor necrosis factor-α,interleukin(IL)-6,IL-1,and briefly IL-18 among proinflammatory cytokines.We update their role in NAFLD,as elucidated in experimental models and clinical practice.展开更多
According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when c...According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.展开更多
Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show bio...Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.展开更多
AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicat...AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.展开更多
Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response ag...Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.展开更多
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not b...Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.展开更多
AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patient...AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patients with active CD(A-CD), or CD in remission(R-CD) and from healthy controls(HCs). The levels of the inflammatory cytokines interleukin-17(IL-17), tumour necrosis factor-α(TNF-α), and interferon-γ(IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of mi R-125 a/b was assessed by quantitative polymerase chain reaction(q PCR).RESULTS Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma mi R-125 a expression was decreased in A-CD patients comparedwith that in R-CD patients(P < 0.001) and HCs(P < 0.001). mi R-125 a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve(AUC) = 0.854] and from HCs(AUC = 0.780), whereas mi R-125 b expression did not. mi R-125 a was negatively correlated with C-reaction protein(CRP)(P = 0.017), erythrocyte sedimentation rate(ESR)(P = 0.026), Crohn's disease activity index(CDAI)(P = 0.003), IL-17(P = 0.015), and TNF-α(P = 0.004) in A-CD patients. Furthermore, mi R-125 a was negatively associated with CRP(P = 0.038) and CDAI(P = 0.021) in R-CD patients. Regarding mi R-125 b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. mi R-125 a levels gradually increased in A-CD patients who achieved clinical remission(P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in mi R-125 b expression were detected in remission or non-remission patients after treatment. CONCLUSION Circulating mi R-125 a but not mi R-125 b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.展开更多
基金supported by the National Natural Science Foundation of China,No.81671347(to KL)the Science and Technology Program of Guangzhou of China,No.202007030012(to KFS and KL)the Science and Technology Program of Guangzhou of China,No 202102020735(to RW).
文摘Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.
文摘The expression and clinical significance of relevant cytokines in otitis media (OM) are discussed, and the alterations to the pathological state of the otitis media mucosa are further understood through the study of cytokine transduction pathways. More and more studies have shown that relevant cell proliferation and inflammation progression pathways play a role in the development of otitis media, such as the Jun amino-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway, the NF-κB signaling pathway, and the PI3K/AKT/PTEN pathway, which are involved in the proliferation of the middle ear mucosa during otitis media, which affects the mucosal cilia, motor function, Eustachian tube function, and the mucosal ciliary function. These studies provide new ideas for the treatment of otitis media and further explore the feasibility of immunotherapy in the future treatment of otitis media. In this paper, we present a review of the latest research progress on the expression of various cytokines in otitis media.
基金the Youth Project of Changzhou Health Commission,No.QN202129.
文摘BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.
基金the Interdisciplinary Program of Shanghai Jiao Tong University(grant nos.YG2019QNB10 and YG2021QN67)Shanghai Municipal Key Clinical Specialty(grant no.shslczdzk00901)Shanghai Municipal Commission of Health and Family Planning(grant no.202240150)。
文摘Background:Acne vulgaris(AV)is a common inflammatory skin disease.Although various mechanisms have been indicated in the etiopathogenesis of AV,the exact pathophysiology remains unknown.Various lasers have been used to treat AV;however,the serum level changes of inflammatory cytokines after laser therapy have not been elucidated.We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595-and 1064-nm dualwavelength laser.Methods:In total,18 patients(9 male and 9 female)between 16 and 35 years of age with moderate to severe AV were evaluated in the study.Disease severity was classified according to the Pillsbury grading system of acne.Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment.A 3 mL blood sample was drawn from every subject each time,and serum levels of inflammatory cytokines such as interleukin(IL)-6,IL-8,and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment.Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation.Results:Inflammation was significantly reduced on both the treated and untreated sides,and symptoms of AV lesions were alleviated.All patients showed a significant increase in serum IL-22 levels after the first laser therapy,with no significant difference in serum IL-6 and IL-8 levels.After the second laser therapy,serum IL-6,IL-8,and IL-22 levels were significantly decreased.No significant side effects such as bruising,edema,hyperpigmentation,hypopigmentation,or scarring were reported.Conclusion:Half-face treatment with 595-and 1064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission,which was associated with a gradual decrease in IL-6,IL-8,and IL-22 levels after half-face topical treatment.This suggests that reducing inflammatory cytokine levels in the serum can relieve inflammation in non-therapeutic sites.This laser treatment is effective,economical,and painless.
文摘The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled.To control cognitive function and behavior,the two systems are engaged in a subtle interacting act.In this scenario,a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging.Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes.In this dynamic equilibrium,synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro-and anti-inflammatory molecules in the central nervous system microenvironment.
文摘Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.
文摘Myelomeningocele(MMC)is a severe form of spinal dysraphism.Due to the failure of neural tube closure during early embryonic development,the affected part of the spinal cord is left open like a book at the back of the affected child.This malformed part of the spinal cord is not covered by its protective mesodermal and ectodermal derived layers.Consequently,the exposed neural tissue(i.e.,the neural placode)is prone to injuryduring further intra-uterine development.
基金Supported by the Intramural Grant IMR Rai 12397B from the Western University of Health Sciences,Pomona,Californiathe Grants from the National Institutes of Health,United States,R01 HL144125 and R01 HL147662.
文摘Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.
基金Lv Jingshan Acupuncture and Medicine Combination Technology Innovation Team(No.2019TD-003)Lv Jingshan Acupuncture and Moxibustion and Bioelectronic Medicine Innovation Team(No.2022TD-1006)。
文摘Objective:To explore the effect of"Yingxiang-Hegu"on Th1,Th2-related cytokines and[2]transcription factors T-bet and GATA-3 in rats with allergic rhinitis.Methods:Rats were randomly divided into three groups:blank group,model group and acupoint group.The rat model of ovalbumin(OVA)AR was established,and the general condition of the rats was observed and scored.Acupuncture intervention was performed on the acupoint group on the second day after successful modeling,once per day for 20 min for 10 d.After intervention,the general behavior,behavioral score and histomorphological changes of nasal mucosa were observed.Eosinophils(EOS)were counted under microscope after nasal lavage smear staining,and the contents of total IgE,IFN-γ,IL-12,IL-4 and IL-5 in serum were detected by ELISA.Westernblot and IHC were used to detect the protein level and positive protein expression of specific transcription factors T-bet and GATA-3 in rat nasal mucosa.Results:After the establishment of the model,except for the blank group,the behavioral observation scores of rats in the model group and acupoint group were more than 5 points,indicating that the model was successful.After acupuncture intervention on acupoint"Yingxiang-Hegu",the behavioral score of rats in the acupoint group and western medicine group was significantly lower than that in the model group(P<0.05).Microscopic examination showed that the structure of nasal mucosa in the model group was obviously damaged,cilia were arranged discontinuously,uneven,local congestion and swelling,a large number of epithelial cells exfoliated and necrotic,goblet cell proliferation,obvious inflammatory cell infiltration.The pathological degree of nasal mucosa in the pair point group was significantly less than that in the model group.Compared with the model group,the levels of IFN-γ,IL-2 and IL-12 in serum were significantly increased,while IgE,IL-4,IL-5 and IL-6 were significantly decreased,GATA-3 protein and positive expression in nasal mucosa were significantly decreased and T-bet was significantly increased after acupuncture.Conclusion:Acupuncture at"Yingxiang-Hegu"can effectively improve the nasal sensitive symptoms and control nasal inflammation in AR rats.The mechanism may be that acupuncture at Yingxiang-Hegu can up-regulate the expression of T-bet,decrease the level of GATA-3,promote the production of Th1 cytokines and inhibit the synthesis and secretion of Th2 cells,thus restoring the immune balance of Th1 and Th2.
文摘Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 nasopharyngeal carcinoma patients with oral mucositis after intensity-modulated radiation therapy(IMRT)were randomly divided into the control group(CG)and the observation group(OG),with 42 cases in each group.The CG was given LLLT,and the OG was treated with Kangfuxin Solution in addition to LLLT for 10 consecutive days.The healing time of oral mucosa,mucositis grading,oral pain scores,cytokines(interleukin-6,interleukin-1βand tumor necrosis factor-α)and T lymphocyte subsets were compared between the 2 groups before and after treatment.Results:The healing time of oral mucosa in the OG was(6.8±1.4)d,which was significantly shorter than(8.6±1.9)d in the CG(t=4.943,P<0.01).After treatment,the grading of oral mucositis in the OG was better than that in the CG,with a statistically significant difference(Z=2.942,P<0.05).The oral pain scores of the OG was lower than that in the CG at different time points after treatment,and the difference was statistically significant(t=8.207,11.017,P<0.01).After treatment,the levels of IL-6,IL-1βand TNF-αin peripheral blood of the OG were significantly lower than those in the CG(t=5.217,2.775,4.053,P<0.01).There were statistically significant differences in CD4+,CD8+and CD4+/CD8+between the OG and the CG after treatment(t=5.692,6.093,3.658,P<0.01).Conclusion:Kangfuxin Solution combined with LLLT can significantly shorten the healing time of oral mucosal,reduce the grading of oral mucositis,relieve oral pain,reduce inflammatory response and improve the immune function of patients.
基金Supparted by the Ntiona1 Natura1 Science Foundation of China No.39670899.
文摘AIM To observe the effect of acupuncture and moxibustion on the expression of IL 1β and IL 6 mRNA in ulcerative colitis rats. METHODS The SD rat ulcerative colitis model was created by immunological method associated with local stimulation. Colonic mucosa was prepared from human fresh surgical colonic specimens, homogenized by adding appropriate amount of normal saline and centrifuged at 3000*!r/*!min . The supernatant was collected for measurement of protein conentration and then mixed with Freund adjuvant. This antigen fluid was first injected into the plantae of the model group rats, and then into their plantae, dorsa, inguina and abdominal cavities (no Freund adjuvant for the last injection) again on the 10th, 17th, 24th and 31st day. When a certain titer of serum anti colonic antibody was reached, 2% formalin and antigen fluid (no Freund adjuvant) were administered separately by enema. The ulcerative colitis rat model was thus set up. The animals were randomly divided into four groups: model control group (MC, n =8), electro acupuncture group (EA, n =8), herbs partition moxibustion group (HPM 8), normal control group (NC, n =8). HPM: Moxa cones made of refined mugwort floss were placed on the medicinal pad (medicinal pad dispensing: Radix Aconiti praeparata, cortex Cinnamomi, etc ) for Qihai (RN 6) and Tianshu (ST 25, bilateral) and ignited. Two moxa cones were used for each acupoint once a day and 14 times in all. EA: Tianshu (bilateral) and Qihai were stimulated by the intermittent pulse with 2Hz frequency, 4mA intensity for 20 minutes once a day and 14 times in all. After treatment, rats of all four groups were killed simultaneously. The spleen was separated and the distal colon was dissected. Total tissue RNA was isolated by the guanidinium thiocyanate phenol chloroform extraction method. RT PCR technique was used to study the expression of IL 1β and IL 6 mRNA. RESULTS IL 1β and IL 6 mRNAs were not detected in the spleen and colonic mucosa of the NC rats, whereas they were significantly expressed in that of the MC rats. IL 1β and IL 6 mRNAs were markedly lower in the EA and HPM rats than that in MC rats. There was no significant difference between the levels of IL 1β and IL 6 mRNAs in the EA and HPM rats. The expressions of IL 1β and IL 6 mRNAs were nearly the same in the spleen and colon of all groups. CONCLUSION Acupuncture and moxibustion greatly inhibited the expression of IL 1β and IL 6 mRNA in the experimental ulcerative colitis rats.
文摘Nonalcoholic fatty liver disease(NAFLD)is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis.The pathogenesis of NAFLD and nonalcoholic steatohepatitis(NASH)has not been fully elucidated.The"two-hit"hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH.It should be better regarded as a multiple step process,with accumulation of liver fat being the first step,followed by the development of necroinflammation and fibrosis.Adipose tissue,which has emerged as anendocrine organ with a key role in energy homeostasis,is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins.These adipocyte-specific or enriched proteins,termed adipokines,have been shown to have a variety of local,peripheral,and central effects.In the current review,we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD.We particularly focus on adiponectin,leptin and ghrelin,with a brief mention of resistin,visfatin and retinol-binding protein 4 among adipokines,and tumor necrosis factor-α,interleukin(IL)-6,IL-1,and briefly IL-18 among proinflammatory cytokines.We update their role in NAFLD,as elucidated in experimental models and clinical practice.
文摘According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.
基金Supported by Ratchadapiseksompotch Fund(RA55/22)Faculty of Medicine,Chulalongkorn University and Office of the Higher Education Commission(CU-NRU,Aging Society Cluster)
文摘Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.
基金Supported by The Grant of Medicine and Health Key Projects of Zhejiang Province, Science and Technology Fund of Ministry of Health of the People’s Republic of China, No. WKJ2007-2-037Shaoxing Key Project for Science and Technology, No. 2007A23008the Natural Science Foundation of Zhejiang Province, China, No. Y2090337
文摘AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.
文摘Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2017R1D1A1B03033271,to JDK)the Bio-Synergy Research Project(NRF-2018M3A9C4076478,to IJK)of the Ministry of Science,ICT and Future Planning through the National Research Foundation
文摘Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.
文摘AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patients with active CD(A-CD), or CD in remission(R-CD) and from healthy controls(HCs). The levels of the inflammatory cytokines interleukin-17(IL-17), tumour necrosis factor-α(TNF-α), and interferon-γ(IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of mi R-125 a/b was assessed by quantitative polymerase chain reaction(q PCR).RESULTS Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma mi R-125 a expression was decreased in A-CD patients comparedwith that in R-CD patients(P < 0.001) and HCs(P < 0.001). mi R-125 a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve(AUC) = 0.854] and from HCs(AUC = 0.780), whereas mi R-125 b expression did not. mi R-125 a was negatively correlated with C-reaction protein(CRP)(P = 0.017), erythrocyte sedimentation rate(ESR)(P = 0.026), Crohn's disease activity index(CDAI)(P = 0.003), IL-17(P = 0.015), and TNF-α(P = 0.004) in A-CD patients. Furthermore, mi R-125 a was negatively associated with CRP(P = 0.038) and CDAI(P = 0.021) in R-CD patients. Regarding mi R-125 b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. mi R-125 a levels gradually increased in A-CD patients who achieved clinical remission(P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in mi R-125 b expression were detected in remission or non-remission patients after treatment. CONCLUSION Circulating mi R-125 a but not mi R-125 b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.
