After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been full...After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.展开更多
BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologi...BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.展开更多
AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplanta...AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.展开更多
AIM:To investigate the associations of interleukin-17(IL-17)genetic polymorphisms and serum levels with ulcerative colitis(UC)risk.METHODS:Relevant articles were identified through a search of the following electronic...AIM:To investigate the associations of interleukin-17(IL-17)genetic polymorphisms and serum levels with ulcerative colitis(UC)risk.METHODS:Relevant articles were identified through a search of the following electronic databases,excluding language restriction:(1)the Cochrane Library Database(Issue 12,2013);(2)Web of Science(1945-2013);(3)PubMed(1966-2013);(4)CINAHL(1982-2013);(5)EMBASE(1980-2013);and(6)the Chinese Biomedical Database(1982-2013).Meta-analysis was conducted using STATA 12.0 software.Crude odds ratios and standardized mean differences(SMDs)with corresponding95%confidence intervals(CIs)were calculated.All of the included studies met all of the following five criteria:(1)the study design must be a clinical cohort or a case-control study;(2)the study must relate to the relationship between IL-17A/F genetic polymorphismsor serum IL-17 levels and the risk of UC;(3)all patients must meet the diagnostic criteria for UC;(4)the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels;and(5)the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium(HWE).The Newcastle-Ottawa Scale(NOS)criteria were used to assess the methodological quality of the studies.The NOS criteria included three aspects:(1)subject selection:0-4;(2)comparability of subjects:0-2;and(3)clinical outcome:0-3.NOS scores ranged from 0 to 9,with a score≥7 indicating good quality.RESULTS:Of the initial 177 articles,only 16 case-control studies met all of the inclusion criteria.A total of1614 UC patients and 2863 healthy controls were included in this study.Fourteen studies were performed on Asian populations,and two studies on Caucasian populations.Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models(P<0.001 for all).The results also showed that UC patients had higher serum IL-17 levels than healthy controls(SMD=5.95,95%CI:4.25-7.65,P<0.001).Furthermore,serum IL-17 levels significantly correlated with the severity of UC(moderate vs mild:SMD=2.59,95%CI:0.03-5.16,P<0.05;severe vs mild:SMD=7.09,95%CI:3.96-10.23,P<0.001;severe vs moderate:SMD=5.84,95%CI:5.09-6.59,P<0.001).The NOS score was≥5 for all of the included studies.Based on the sensitivity analysis,no single study influenced the overall pooled estimates.Neither the Begger’s funnel plots nor Egger’s test displayed strong statistical evidence for publication bias(IL-17A/F genetic polymorphisms:t=-2.60,P=0.019;serum IL-17 levels:t=-1.54,P=0.141).CONCLUSION:The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC.展开更多
Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced...Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced by dextran sulfate sodium(DSS),and mice were divided into 4 groups:control.DSS alone.DSS plus SASP,DSS plus pectic polysaccharides.The disease activity index(DAI) and histological score were observed.The tumor necrosis factor(TNF)-α and interleukin(IL)-17 levels were measured by enzyme-linked immunosorbent assay.I κ B and NF-κB p65 expression were assessed by western blot analysis.Myeloperoxidase(MPO) activity was determined by using MPO assay kit.Re.sults:Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAT and histological score,and resulted in down regulation of MPO activity and NF-κB p65 expression and subsequent degradation of IκB protein,strikingly reduced the production of TNF-α and IL-17.Conclusions:Pectic polysaccharides extracted from Rauvolfia verticillata(Lour.)Baill.var.hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.展开更多
AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 ...AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.展开更多
Innate-like T cells, namely natural killer T(NKT) and γδ T cells, play critical roles in linking innate and adaptive immune responses through rapid production of cytokines. Prominent among these cytokines is interle...Innate-like T cells, namely natural killer T(NKT) and γδ T cells, play critical roles in linking innate and adaptive immune responses through rapid production of cytokines. Prominent among these cytokines is interleukin-17(IL-17), which is a potent proinflammatory cytokine that plays a critical role in host defense against fungi and extracellular bacteria. However, excessive IL-17-production promotes autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. IL-17 has also been implicated in regulating body fat, which is highly relevant given rises in obesity and type 2 diabetes. NKT cells, γδ T cells and mucosal-associated invariant T cells(MAIT) are the major sources of IL-17 involved in protection of mucosal surfaces from opportunistic infections and causing autoimmunity when become dysregulated. Given the pathogenic effects of IL-17, efforts have been directed towards understanding mechanisms that guard against IL-17 overproduction. One novel potent mechanism is mediated by the heparan sulfate proteoglycan, syndecan-1(sdc1), which is selectively expressed by IL-17-producing subsets of NKT and γδ T cells. This unexpected role for sdc1 is uncovered by analysis of NKT and γδ T cells in sdc1-deficient mice. In this mini-review, we discuss selective expression of sdc1 by these innate T cells and consequences of its absence on IL-17 homeostasis and pathological implications.展开更多
Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury.The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules re...Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury.The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response.Interleukin(IL)-17A,produced in the early phase of inflammation,influences the fate of osteoprogenitors.Due to their inherent capacity to differentiate into osteoblasts,mesenchymal stem/stromal cells(MSCs)contribute to bone healing and regeneration.This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs.The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described.To this end,divergent information exists about the capacity of IL-17A to regulate MSCs’osteogenic fate,depending on the tissue context and target cell type,along with contradictory findings in the same cell types.Therefore,we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17,which may help in the understanding of IL-17A function in bone repair and regeneration.展开更多
Background Recent studies have also revealed that interleukin(IL)-17A plays a key role in atherosclerosis and its complication,but the relationship of its common variants with coronary artery disease(CAD) has not been...Background Recent studies have also revealed that interleukin(IL)-17A plays a key role in atherosclerosis and its complication,but the relationship of its common variants with coronary artery disease(CAD) has not been extensively studied.Methods We systematically screened sequence variations in the IL17A gene and designed an angiog-raphy -based case-controlled study consisting of 1031 CAD patients and 935 control subjects to investigate the association between the selected polymorphisms of IL-17A gene and CAD risk in Chinese Han population.Results Frequencies of IL17A rs8193037 GG homozygote and G allele were significantly higher in the patient group than those in the control group(P【0.001;OR=0.68;95%CI=0.54-0.85).Stratification analysis showed that the IL17A rs8193037 G allele significantly increased the risk of CAD only among male subjects (P=0.001;OR=0.63;95%CI=0.47-0.83).After adjustment for conventional risk factors,binary logistic regression analysis showed that the G allele carriers(GG +AG) had significantly increased CAD risk compared with the AA homozygotes (adjusted P【0.001;OR 0.43;95%CI,0.33- 0.58).ELISA showed augmented IL17A production in plasma of the AMI patients.Conclusions Based on our data,we speculated that the SNP rs8193037 of IL17A gene is significantly associated with CAD risk in Chinese Han population and the rs8193037 G allele which is associated with increased expression of IL17A in AMI patients may be an independent predictive factor for CAD.展开更多
Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin o...Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin of CSCs is still unclear,but it has been recently suggested that CSCs could originate from the transformation of liver progenitor cells(LPCs)during chronic liver inflammation.展开更多
Natural killer T cells(NKT cells) are innate-like T cells that acquire effector functions while developing in the thymus, polarize into three distinct functional subsets viz. NKT1, NKT2 and NKT17 cells that produce in...Natural killer T cells(NKT cells) are innate-like T cells that acquire effector functions while developing in the thymus, polarize into three distinct functional subsets viz. NKT1, NKT2 and NKT17 cells that produce interferon(IFN)-γ, interleukin(IL)-4 and IL-17, respectively. However, there has been no unique surface markers that define each subsets, forcing investigators to use intracellular staining of transcription factors and cytokines in combination of surface markers to distinguish among these subsets. Intracellular staining, however, causes apoptosis and prevents subsequent utilization of NKT cells in functional in vitro and in vivo assays that require viable cells. This limitation has significantly impeded understanding the specific properties of each subset and their interactions with each other. Therefore, there has been fervent efforts to find a specific markers for each NKT cell subset. We have recently identified that syndecan-1(SDC-1; CD138) as a specific surface marker of NKT17 cells. This discovery now allows visualization of NKT17 in situ and study of their peripheral tissue distribution, characteristics of their TCR and viable sorting for in vitro and in vivo analysis. In addition, it lays the ground working for investigating significance of SDC-1 expression on this particular subset in regulating their roles in host defense and glucose metabolism.展开更多
AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtai...AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 μg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori(H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26 695 or recombinant human (rh) IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2 499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P<0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1356 pg/mg/protein, range 121-1 3730; antrum: median 761 pg/mg/protein, range 24-7 620, P<0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r= 0.62, P<0.0001; antrum: r = 0.61, P<0.0001) in GU patients. RhIL-17 and H pylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.展开更多
AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response media...AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.展开更多
The expression of interleukin-17(IL-17) in lung and peripheral blood of asthmatic rats and the influence of dexamethasone,and the role of IL-17 in the pathogenesis of asthma were investigated.Thirty Sprague-Dawley(SD)...The expression of interleukin-17(IL-17) in lung and peripheral blood of asthmatic rats and the influence of dexamethasone,and the role of IL-17 in the pathogenesis of asthma were investigated.Thirty Sprague-Dawley(SD) adult rats were randomly divided into three groups(n=10 in each group):normal group,asthmatic group,and dexamethasone-interfered group.Rat asthmatic model was established by intraperitoneal(i.p.) injection of 10% ovalbumin(OVA) and challenge with 1% OVA via inhalation.Rats in dexamethasone-interfered group were pretreated with dexamethasone(2 mg/kg,i.p.) 30 min before each challenge.The expression of IL-17 protein in serum and bronchoalveolar lavage fluid(BALF) was detected by ELISA.The expression of IL-17 mRNA in peripheral blood mononuclear cells(PBMC) and BALF cells was semi-quantitatively detected by RT-PCR.The expression of IL-17 protein in serum and BALF of asthmatic rats was significantly elevated as compared with normal rats and dexamethsone-interfered rats(P<0.01),and there was significant difference between normal rats and dexamethsone-interfered rats(P<0.05).The expression of IL-17 mRNA in PBMC and BALF cells of asthmatic rats was markedly increased as compared with normal rats and dexamethsone-interfered rats(P<0.01),and significant difference was found between normal rats and dexamethsone-interfered rats(P<0.05).It was concluded that the expression of IL-17 was increased significantly in asthmatic rats and could be inhibited partly by dexamethasone,suggesting that IL-17 might play an important role in the pathogenesis of asthma as an inflammation regulation factor.展开更多
Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain rea...Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.展开更多
Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 ...Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.展开更多
Objective To study the potential role of macrophage migration inhibitory factor(MIF),Interleukin-17(IL-17) and Interleukin-10(IL-10) in the development of HBV-related liver disease.Methods 48 patients with chronic hep...Objective To study the potential role of macrophage migration inhibitory factor(MIF),Interleukin-17(IL-17) and Interleukin-10(IL-10) in the development of HBV-related liver disease.Methods 48 patients with chronic hepatitis B(HBeAg negative and positive,24 cases;21cases of HBV-DNA negative and 27 cases of HBV-DNA positive),81 cases of hepatitis B patients with decompensated cirrhosis and 48 cases of primary liver cancer patients were collected as the experimental group,26 healthy people were as control group.Serum MIF,IL-17 and IL-10 were measured.Results MIF and IL-17 significantly increased,IL-10 significantly decreased in experimental group,compared with the control group(P<0.05),there was significant difference.In addition,there was no significant difference(P>0.05) between positive and negative of chronic hepatitis B.MIF,IL-17 and ALT levels were positively correlated(r=0.693,P<0.01;r=0.897,P<0.001),IL-10 and ALT was negatively correlated(r =-0.285,P=0.037).Conclusion These results indicated that MIF,IL-17 and IL-10 may participate in the pathological process of HBV-related liver disease,serum levels of MIF,IL-17 and IL-10 appear to reflect the severity of tissue injury in HBV-related liver disease.展开更多
AIM:To evaluate the proinflammatory effects and molecular mechanisms of interleukin(IL)-17 in intestinal epithelial cell line HT-29.METHODS:HT-29 cells were cultured with IL-17,tumor necrosis factor(TNF)-α,or the com...AIM:To evaluate the proinflammatory effects and molecular mechanisms of interleukin(IL)-17 in intestinal epithelial cell line HT-29.METHODS:HT-29 cells were cultured with IL-17,tumor necrosis factor(TNF)-α,or the combination of both IL-17 and TNF-α.Real-time PCR and Western blot were used to measure the gene expression levels of neutrophil chemokines CXCL1,CXCL2,CXCL5,CXCL6,IL-8and TH-17 cell chemokine CCL20,the phosphorylation levels of p38 and TNF-α,and the expression level of IL-8,after using the p38 inhibitor in HT-29 cells.The stable Act1 knockdown HT-29 cell line was established to further test the phosphorylation changes of p38,after using IL-17 and TNF-α.RESULTS:After HT-29 cells were cultured with IL-17and TNF-α,the expression levels of neutrophil chemokines(CXCL1,CXCL2,CXCL5,CXCL6,IL-8)and Th17chemokine(CCL20)significantly improved(24.96±2.53,28.47±2.87,38.08±2.72,33.47±2.41,31.7±2.38,44.37±2.73,respectively),and the differences were all statistically significant(P<0.01).Western blot results showed that IL-17 obviously enhanced the phosphorylation level of p38,which was induced by TNF-α.Compared with the control group,the expression level of IL-8 significantly declined(9.47±1.36 vs 3.06±0.67,P<0.01)when TH-29 cells were cultured with IL-17and TNF-α.p38 inhibition assay showed that the p38pathway played an essential role in the inflammatory response induced by IL-17.p38 phosphorylation levels could not be changed after using IL-17 and TNF-αin the stable Act1 knockdown HT-29 cell line.CONCLUSION:IL-17 significantly promoted the gene expression levels of TNF-α-induced neutrophil chemokines and Th17 cell chemokine.It is obvious that IL-17and TNF-αhave synergistic effects on p38.展开更多
Interleukin-17(IL-17),a prototype member of IL-17 family,plays an important role in defending against extracellular pathogens as a pro-inflammatory cytokine.The function and distribution of IL-17 have been extensively...Interleukin-17(IL-17),a prototype member of IL-17 family,plays an important role in defending against extracellular pathogens as a pro-inflammatory cytokine.The function and distribution of IL-17 have been extensively studied in many vertebrates.However,few study has focused on the role of IL-17 in invertebrates,especially in mollusks.In this study,an IL-17 homolog was identified in Octopus ocellatus,which was designated as OoIL-17.The phylogenetic analysis showed that OoIL-17 is clustered well with other invertebrate IL-17,indicating it is highly similar with the IL-17 of other invertebrates.The expression of OoIL-17 gene was analyzed with qRT-PCR in a variety of healthy tissues and the hemocytes infected with Vibro anguillarum or Micrococcus luteus.The mRNA of OoIL-17 gene is constitutively expressed at different levels in all examined tissues of healthy O.ocellatus,including mantle,stomach,hemocytes,muscle,gonad,hepatopancreas,systemic heart and gill.The lowest expression was observed in mantle while the highest was observed in hepatopancreas.The expression level of OoIL-17 gene is significantly up-regulated in O.ocellatus hemocytes upon infection with V.anguillarum and M.luteus,indicating its active involvement in the host immune response against bacterial pathogens.The results laid the foundation for further understanding the innate immune mechanisms of IL-17 in O.ocellatus and mollusks.展开更多
基金supported by the National Natural Science Foundation of China,No. 81771327 (to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research PlatformBudget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (BYL)。
文摘After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.
文摘BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.
基金Supported by Grants from Scientific Technology Research Development Project of Shaanxi in part,No.2011K14-05-01,No.2008K12-01a Grant from the National Natural Scientific Foundation of China,No.31100643
文摘AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.
文摘AIM:To investigate the associations of interleukin-17(IL-17)genetic polymorphisms and serum levels with ulcerative colitis(UC)risk.METHODS:Relevant articles were identified through a search of the following electronic databases,excluding language restriction:(1)the Cochrane Library Database(Issue 12,2013);(2)Web of Science(1945-2013);(3)PubMed(1966-2013);(4)CINAHL(1982-2013);(5)EMBASE(1980-2013);and(6)the Chinese Biomedical Database(1982-2013).Meta-analysis was conducted using STATA 12.0 software.Crude odds ratios and standardized mean differences(SMDs)with corresponding95%confidence intervals(CIs)were calculated.All of the included studies met all of the following five criteria:(1)the study design must be a clinical cohort or a case-control study;(2)the study must relate to the relationship between IL-17A/F genetic polymorphismsor serum IL-17 levels and the risk of UC;(3)all patients must meet the diagnostic criteria for UC;(4)the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels;and(5)the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium(HWE).The Newcastle-Ottawa Scale(NOS)criteria were used to assess the methodological quality of the studies.The NOS criteria included three aspects:(1)subject selection:0-4;(2)comparability of subjects:0-2;and(3)clinical outcome:0-3.NOS scores ranged from 0 to 9,with a score≥7 indicating good quality.RESULTS:Of the initial 177 articles,only 16 case-control studies met all of the inclusion criteria.A total of1614 UC patients and 2863 healthy controls were included in this study.Fourteen studies were performed on Asian populations,and two studies on Caucasian populations.Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models(P<0.001 for all).The results also showed that UC patients had higher serum IL-17 levels than healthy controls(SMD=5.95,95%CI:4.25-7.65,P<0.001).Furthermore,serum IL-17 levels significantly correlated with the severity of UC(moderate vs mild:SMD=2.59,95%CI:0.03-5.16,P<0.05;severe vs mild:SMD=7.09,95%CI:3.96-10.23,P<0.001;severe vs moderate:SMD=5.84,95%CI:5.09-6.59,P<0.001).The NOS score was≥5 for all of the included studies.Based on the sensitivity analysis,no single study influenced the overall pooled estimates.Neither the Begger’s funnel plots nor Egger’s test displayed strong statistical evidence for publication bias(IL-17A/F genetic polymorphisms:t=-2.60,P=0.019;serum IL-17 levels:t=-1.54,P=0.141).CONCLUSION:The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC.
基金supported by National Natural Science Foundation of China(Grant No.81360603)Natural Science Foundation of Hainan Province(Grant No.813215)
文摘Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced by dextran sulfate sodium(DSS),and mice were divided into 4 groups:control.DSS alone.DSS plus SASP,DSS plus pectic polysaccharides.The disease activity index(DAI) and histological score were observed.The tumor necrosis factor(TNF)-α and interleukin(IL)-17 levels were measured by enzyme-linked immunosorbent assay.I κ B and NF-κB p65 expression were assessed by western blot analysis.Myeloperoxidase(MPO) activity was determined by using MPO assay kit.Re.sults:Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAT and histological score,and resulted in down regulation of MPO activity and NF-κB p65 expression and subsequent degradation of IκB protein,strikingly reduced the production of TNF-α and IL-17.Conclusions:Pectic polysaccharides extracted from Rauvolfia verticillata(Lour.)Baill.var.hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.
基金Supported by The Mazandaran University of Medical Sciences,No.89-512
文摘AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.
文摘Innate-like T cells, namely natural killer T(NKT) and γδ T cells, play critical roles in linking innate and adaptive immune responses through rapid production of cytokines. Prominent among these cytokines is interleukin-17(IL-17), which is a potent proinflammatory cytokine that plays a critical role in host defense against fungi and extracellular bacteria. However, excessive IL-17-production promotes autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. IL-17 has also been implicated in regulating body fat, which is highly relevant given rises in obesity and type 2 diabetes. NKT cells, γδ T cells and mucosal-associated invariant T cells(MAIT) are the major sources of IL-17 involved in protection of mucosal surfaces from opportunistic infections and causing autoimmunity when become dysregulated. Given the pathogenic effects of IL-17, efforts have been directed towards understanding mechanisms that guard against IL-17 overproduction. One novel potent mechanism is mediated by the heparan sulfate proteoglycan, syndecan-1(sdc1), which is selectively expressed by IL-17-producing subsets of NKT and γδ T cells. This unexpected role for sdc1 is uncovered by analysis of NKT and γδ T cells in sdc1-deficient mice. In this mini-review, we discuss selective expression of sdc1 by these innate T cells and consequences of its absence on IL-17 homeostasis and pathological implications.
基金Supported by Ministry of Education,Science and Technological Development of Serbia,No.451-03-9/2021-14/200015and Oesterreichische Nationalbank(Austrian Central Bank,Anniversary Fund),No.18517(to KrstićJ).
文摘Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury.The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response.Interleukin(IL)-17A,produced in the early phase of inflammation,influences the fate of osteoprogenitors.Due to their inherent capacity to differentiate into osteoblasts,mesenchymal stem/stromal cells(MSCs)contribute to bone healing and regeneration.This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs.The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described.To this end,divergent information exists about the capacity of IL-17A to regulate MSCs’osteogenic fate,depending on the tissue context and target cell type,along with contradictory findings in the same cell types.Therefore,we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17,which may help in the understanding of IL-17A function in bone repair and regeneration.
文摘Background Recent studies have also revealed that interleukin(IL)-17A plays a key role in atherosclerosis and its complication,but the relationship of its common variants with coronary artery disease(CAD) has not been extensively studied.Methods We systematically screened sequence variations in the IL17A gene and designed an angiog-raphy -based case-controlled study consisting of 1031 CAD patients and 935 control subjects to investigate the association between the selected polymorphisms of IL-17A gene and CAD risk in Chinese Han population.Results Frequencies of IL17A rs8193037 GG homozygote and G allele were significantly higher in the patient group than those in the control group(P【0.001;OR=0.68;95%CI=0.54-0.85).Stratification analysis showed that the IL17A rs8193037 G allele significantly increased the risk of CAD only among male subjects (P=0.001;OR=0.63;95%CI=0.47-0.83).After adjustment for conventional risk factors,binary logistic regression analysis showed that the G allele carriers(GG +AG) had significantly increased CAD risk compared with the AA homozygotes (adjusted P【0.001;OR 0.43;95%CI,0.33- 0.58).ELISA showed augmented IL17A production in plasma of the AMI patients.Conclusions Based on our data,we speculated that the SNP rs8193037 of IL17A gene is significantly associated with CAD risk in Chinese Han population and the rs8193037 G allele which is associated with increased expression of IL17A in AMI patients may be an independent predictive factor for CAD.
文摘Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin of CSCs is still unclear,but it has been recently suggested that CSCs could originate from the transformation of liver progenitor cells(LPCs)during chronic liver inflammation.
文摘Natural killer T cells(NKT cells) are innate-like T cells that acquire effector functions while developing in the thymus, polarize into three distinct functional subsets viz. NKT1, NKT2 and NKT17 cells that produce interferon(IFN)-γ, interleukin(IL)-4 and IL-17, respectively. However, there has been no unique surface markers that define each subsets, forcing investigators to use intracellular staining of transcription factors and cytokines in combination of surface markers to distinguish among these subsets. Intracellular staining, however, causes apoptosis and prevents subsequent utilization of NKT cells in functional in vitro and in vivo assays that require viable cells. This limitation has significantly impeded understanding the specific properties of each subset and their interactions with each other. Therefore, there has been fervent efforts to find a specific markers for each NKT cell subset. We have recently identified that syndecan-1(SDC-1; CD138) as a specific surface marker of NKT17 cells. This discovery now allows visualization of NKT17 in situ and study of their peripheral tissue distribution, characteristics of their TCR and viable sorting for in vitro and in vivo analysis. In addition, it lays the ground working for investigating significance of SDC-1 expression on this particular subset in regulating their roles in host defense and glucose metabolism.
文摘AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 μg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori(H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26 695 or recombinant human (rh) IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2 499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P<0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1356 pg/mg/protein, range 121-1 3730; antrum: median 761 pg/mg/protein, range 24-7 620, P<0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r= 0.62, P<0.0001; antrum: r = 0.61, P<0.0001) in GU patients. RhIL-17 and H pylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.
文摘AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.
文摘The expression of interleukin-17(IL-17) in lung and peripheral blood of asthmatic rats and the influence of dexamethasone,and the role of IL-17 in the pathogenesis of asthma were investigated.Thirty Sprague-Dawley(SD) adult rats were randomly divided into three groups(n=10 in each group):normal group,asthmatic group,and dexamethasone-interfered group.Rat asthmatic model was established by intraperitoneal(i.p.) injection of 10% ovalbumin(OVA) and challenge with 1% OVA via inhalation.Rats in dexamethasone-interfered group were pretreated with dexamethasone(2 mg/kg,i.p.) 30 min before each challenge.The expression of IL-17 protein in serum and bronchoalveolar lavage fluid(BALF) was detected by ELISA.The expression of IL-17 mRNA in peripheral blood mononuclear cells(PBMC) and BALF cells was semi-quantitatively detected by RT-PCR.The expression of IL-17 protein in serum and BALF of asthmatic rats was significantly elevated as compared with normal rats and dexamethsone-interfered rats(P<0.01),and there was significant difference between normal rats and dexamethsone-interfered rats(P<0.05).The expression of IL-17 mRNA in PBMC and BALF cells of asthmatic rats was markedly increased as compared with normal rats and dexamethsone-interfered rats(P<0.01),and significant difference was found between normal rats and dexamethsone-interfered rats(P<0.05).It was concluded that the expression of IL-17 was increased significantly in asthmatic rats and could be inhibited partly by dexamethasone,suggesting that IL-17 might play an important role in the pathogenesis of asthma as an inflammation regulation factor.
文摘Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.
基金supported by the Natural Science Foundation of Anhui Province of China,No.1708085MH211(to HWC)the College Top-notch Talent Foundation of Anhui Province of China,No.KJ2018A0207(to HWC)
文摘Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.
基金supported by grants from the Natural Science Foundation of Gansu Province of China
文摘Objective To study the potential role of macrophage migration inhibitory factor(MIF),Interleukin-17(IL-17) and Interleukin-10(IL-10) in the development of HBV-related liver disease.Methods 48 patients with chronic hepatitis B(HBeAg negative and positive,24 cases;21cases of HBV-DNA negative and 27 cases of HBV-DNA positive),81 cases of hepatitis B patients with decompensated cirrhosis and 48 cases of primary liver cancer patients were collected as the experimental group,26 healthy people were as control group.Serum MIF,IL-17 and IL-10 were measured.Results MIF and IL-17 significantly increased,IL-10 significantly decreased in experimental group,compared with the control group(P<0.05),there was significant difference.In addition,there was no significant difference(P>0.05) between positive and negative of chronic hepatitis B.MIF,IL-17 and ALT levels were positively correlated(r=0.693,P<0.01;r=0.897,P<0.001),IL-10 and ALT was negatively correlated(r =-0.285,P=0.037).Conclusion These results indicated that MIF,IL-17 and IL-10 may participate in the pathological process of HBV-related liver disease,serum levels of MIF,IL-17 and IL-10 appear to reflect the severity of tissue injury in HBV-related liver disease.
基金Supported by Minhang District Natural Science Foundation(to Wang YL)the Science and Technology Commission in Shanghai,No.10411968500 National Natural Science Foundation of China,No.81001324
文摘AIM:To evaluate the proinflammatory effects and molecular mechanisms of interleukin(IL)-17 in intestinal epithelial cell line HT-29.METHODS:HT-29 cells were cultured with IL-17,tumor necrosis factor(TNF)-α,or the combination of both IL-17 and TNF-α.Real-time PCR and Western blot were used to measure the gene expression levels of neutrophil chemokines CXCL1,CXCL2,CXCL5,CXCL6,IL-8and TH-17 cell chemokine CCL20,the phosphorylation levels of p38 and TNF-α,and the expression level of IL-8,after using the p38 inhibitor in HT-29 cells.The stable Act1 knockdown HT-29 cell line was established to further test the phosphorylation changes of p38,after using IL-17 and TNF-α.RESULTS:After HT-29 cells were cultured with IL-17and TNF-α,the expression levels of neutrophil chemokines(CXCL1,CXCL2,CXCL5,CXCL6,IL-8)and Th17chemokine(CCL20)significantly improved(24.96±2.53,28.47±2.87,38.08±2.72,33.47±2.41,31.7±2.38,44.37±2.73,respectively),and the differences were all statistically significant(P<0.01).Western blot results showed that IL-17 obviously enhanced the phosphorylation level of p38,which was induced by TNF-α.Compared with the control group,the expression level of IL-8 significantly declined(9.47±1.36 vs 3.06±0.67,P<0.01)when TH-29 cells were cultured with IL-17and TNF-α.p38 inhibition assay showed that the p38pathway played an essential role in the inflammatory response induced by IL-17.p38 phosphorylation levels could not be changed after using IL-17 and TNF-αin the stable Act1 knockdown HT-29 cell line.CONCLUSION:IL-17 significantly promoted the gene expression levels of TNF-α-induced neutrophil chemokines and Th17 cell chemokine.It is obvious that IL-17and TNF-αhave synergistic effects on p38.
基金supported by the earmarked fund for the Modern Agro-Industry Technology Research System (No. CARS-49)the Natural Science Foundation of Shandong Province (No. ZR2019BC052)the Marine and Fisheries Science and Technology Innovation Program of Shan-dong Province (No. 2017YY04)
文摘Interleukin-17(IL-17),a prototype member of IL-17 family,plays an important role in defending against extracellular pathogens as a pro-inflammatory cytokine.The function and distribution of IL-17 have been extensively studied in many vertebrates.However,few study has focused on the role of IL-17 in invertebrates,especially in mollusks.In this study,an IL-17 homolog was identified in Octopus ocellatus,which was designated as OoIL-17.The phylogenetic analysis showed that OoIL-17 is clustered well with other invertebrate IL-17,indicating it is highly similar with the IL-17 of other invertebrates.The expression of OoIL-17 gene was analyzed with qRT-PCR in a variety of healthy tissues and the hemocytes infected with Vibro anguillarum or Micrococcus luteus.The mRNA of OoIL-17 gene is constitutively expressed at different levels in all examined tissues of healthy O.ocellatus,including mantle,stomach,hemocytes,muscle,gonad,hepatopancreas,systemic heart and gill.The lowest expression was observed in mantle while the highest was observed in hepatopancreas.The expression level of OoIL-17 gene is significantly up-regulated in O.ocellatus hemocytes upon infection with V.anguillarum and M.luteus,indicating its active involvement in the host immune response against bacterial pathogens.The results laid the foundation for further understanding the innate immune mechanisms of IL-17 in O.ocellatus and mollusks.
