BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regen...BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.展开更多
AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained fr...AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.展开更多
The capability of recombinant human interleukin-2 ( rhIL-2) and lymphokine-activated killer (LAK) cells in the purging of normal human bone marrows contaminated with human myeloid leukemic cell lines was evaluated. Mi...The capability of recombinant human interleukin-2 ( rhIL-2) and lymphokine-activated killer (LAK) cells in the purging of normal human bone marrows contaminated with human myeloid leukemic cell lines was evaluated. Mixtures of normal human bone marrow mononuclear cells ( BMC) and K562 cells or HL-60 cells (at the BMCK562 ratio of 200:1, 100:1 or 20:1) were incubated with IL-2 with or without LAK cells at the BMC:LAK ratio of 1:1 for one or three days. The nubmers of residual K562 cells, BFU-E and CFU-GM were examined by clonogenic assays. In 200:1 mixture groups without LAK cells, the number of K562 colonies reduced by 50% with no loss of BFU-E and CFU-GM in one-day cultures, and no K562 colonies formed in three-day cultures with about 20% loss of BFU-E and CFU-GM. If the BMC.K562 ratios were 100:1 or 20:1 in the mktures, the leukemic cells could not be eliminated. When the mixtures were incubated with IL-2 and LAK cells, no leukemic cell colonies were detected in the 20:1 group following one-day展开更多
Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Meth...Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Method 29 patients with active AS were selected to take GTT (1mg per kg) three times a day for one year. After that, its curative effect was evaluated. The serum level of sIL-2R of these patients was measured by sandwich ELISA method and was compared with that of normal subjects. Result The serum level of sIL-2R in active AS patients was obviously higher than that of the non-active AS patients. (P<0.01). The total effective rate of GTT on AS was 89.6%, while clinical relief rate 27.6%, obvious effective rate 44.8%, effective rate 17.2% and non-effective rate 10.4%. The patients’ serum level of sIL-2R after therapy was significantly lower than that before therapy except patients with no effect. (P<0.05). Conclusion GTT has positive curative effect on active AS patients and could cause obvious decrease of the serum level of sIL-2R. The serum level of sIL-2R can be used as an important index of activity of AS and as a guide of therapy.展开更多
INTRODUCTIONMacrophages play an important role in tumor lysisand growth inhibition.They can be activated to atumoricidal state by a variety of agents such asIFNr,TNFα or IL2.The killing machanisms ofactivated macroph...INTRODUCTIONMacrophages play an important role in tumor lysisand growth inhibition.They can be activated to atumoricidal state by a variety of agents such asIFNr,TNFα or IL2.The killing machanisms ofactivated macrophages have been extensivelyinvestigated.Recently,it has been proved thatantibody dependent cellular cytotoxicity (ADCC) isone of the potent arms to lyse tumor cells展开更多
Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the pres...Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.展开更多
Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effect...Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.展开更多
Objective:To investigate the role and the clinical significance of anti-zona pellucidaantibody (AzpAb) and tumor necrosis factor-α(TNF-α),γ-interferon(IFN-γ) and inter-leukin-2 (IL-2) in sera from patients with pr...Objective:To investigate the role and the clinical significance of anti-zona pellucidaantibody (AzpAb) and tumor necrosis factor-α(TNF-α),γ-interferon(IFN-γ) and inter-leukin-2 (IL-2) in sera from patients with premature ovarian failure (POF).Methods: The AzpAb in the serum of POF patient was analyzed by means ofELISA. The levels of TNF-α, IL-2 and IFN-γ in the serum were determined by meansof radioimmunoassay (RIA).Results:The level of serum AzpAb in the POF patients was significantly higher thanthat of the normal controls(P＜0.001). The levels of TNF-α and IL-2 were significantlyreduced (P＜0. 001), and the level of IFN-γ was significantly elevated (P＜0.01). Thelevels of above three cytokines in AzpAb positive group were significantly higher thanthose of the negative group in POF patients.Conclusion: This study suggested that AzpAb, TNF-α, IFN-γ and IL-2 might playimportant roles in the pathogenesis of autoimmune POF.展开更多
AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intr...AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intravenously with Con A at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3(STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein m RNA expression was significantly elevated after IL-22 treatment.CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.展开更多
In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-tal...In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4+ T helper cells co-expressing interferon-γ and follicular T helper cells.Moreover,both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation.In this article,we review the available data supporting the pathogenic role of IL-21 in IBD.展开更多
BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in ge...BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.展开更多
AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin(IL)-24 in hepatocellular carcinoma(HCC) cells.METHODS: γ-secretase inhibitors(GSIs) were used to dow...AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin(IL)-24 in hepatocellular carcinoma(HCC) cells.METHODS: γ-secretase inhibitors(GSIs) were used to down-regulate Notch1.Hep G2 and SMMC7721 cells were seeded in 96-well plates and treated with GSI-I or/and IL-24 for 48 h.Cell viability was measured by MTT assay.The cellular and nuclear morphology was observed under a fluorescence microscope.To further verify the apoptotic phenotype,cell cultures were also analyzed by flow cytometry with Annexin V-FITC/propidium iodide staining.The expression of Notch1,SNAIL1,SNAIL2,E-cadherin,IL-24,XIAP and VEGF was detected by Western blot.The invasion and migration capacities of HCC cells were detected by wound healing assays.Notch1 and Snail were downregulated by RNA interference,and the target proteins were analyzed by Western blot.To investigate the mechanism of apoptosis,we analyzed Hep G2 cells treated with si Notch1 or si CON plus IL-24 or not for 48h by caspase-3/7 activity luminescent assay.RESULTS: GSI-I at a dose of 2.5 μmol/L for 24 h caused a reduction in cell viability of about 38% in Hep G2 cells.The addition of 50 ng/m L IL-24 in combination with 1 or 2.5 μmol/L GSI-I reduced cell viability of about 30% and 15%,respectively.Treatment with IL-24 alone did not induce any cytotoxic effect.In SMMC7721 cells with the addition of IL-24 to GSI-I(2.5 μmol/L),the reduction of cell viability was only about 25%.Following GSI-I/IL-24 combined treatment for 6 h,the apoptotic rate of Hep G2 cells was 47.2%,while no significant effect was observed in cells treated with the compounds employed separately.Decreased expression of Notch1 and its associated proteins SNAIL1 and SNAIL2 was detected in Hep G2 cells.Increased E-cadherin protein expression was noted in the presence of IL-24 and GSI-I.Furthermore,the increased GSI-I and IL-24 in Hep G2 cell was associated with downregulation of MMP-2,XIAP and VEGF.In the absence of treatment,Hep G2 cells could migrate into the scratched space in 24 h.With IL-24 or GSI-I treatment,the wound was still open after 24 h.And the distance of the wound closure strongly correlated with the concentrations of IL-24 and GSI-I.Treatment of Notch-1 silenced Hep G2 cells with 50 ng/m L IL-24 alone for 48 h induced cytotoxic effects very similar to those observed in non-silenced cells treated with GSI-I/IL-24 combination.Caspase-3/7 activity was increased in the presence of si Notch1 plus IL-24 treatment.CONCLUSION: Down-regulation of Notch1 by GSI-I or si RNA combined with IL-24 can sensitize apoptosis and decrease the invasion and migration capabilities of Hep G2 cells.展开更多
AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway invol...AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of har...Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract,leading to further inflammation.Interleukin(IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells.Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3signaling cascades.This cytokine induces antimicrobial m olecules and proliferative and antiapoptoic pathways,which help prevent tissue damage and aid in its repair.All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity.In this review,we discuss recent progress in the involvement of IL-22in the pathogenesis of IBD,as well as its therapeutic potential.展开更多
AIM To investigate interleukin(IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease(IBD) and the function of IL-26. METHODS Human colonic subepithelial myofibroblasts(SEMFs) were isolat...AIM To investigate interleukin(IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease(IBD) and the function of IL-26. METHODS Human colonic subepithelial myofibroblasts(SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by realtime polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering(si) RNA transfection. RESULTS The m RNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the m RNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and si RNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the m RNA expression of IL-6 and IL-8 induced by IL-26.CONCLUSION These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.展开更多
Allergic rhinitis (AR) is the inflammation of nasal mucosa due to the type 1 hypersensitivity reactions mediated by immunoglobulin E (IgE) and triggered by certain allergens. The latest concept in allergic disease is ...Allergic rhinitis (AR) is the inflammation of nasal mucosa due to the type 1 hypersensitivity reactions mediated by immunoglobulin E (IgE) and triggered by certain allergens. The latest concept in allergic disease is the role of regulatory T cells (Treg). Interleukin-2 enhances the function and survival of Treg to perform its function as a controller of effector for forming a tolerant system by suppressing and regulating the homeostasis system. Treg has a transcription factor FoxP3 which plays a role in developing major function of Treg and progression to produce IL-10 and TGF-?. The atopic diseases are caused by a deficiency of Treg. The new perspective is low-dose IL-2 therapy towards autoimmune disease and allergic inflammation. Low-dose IL-2 therapy requires further clinical studies to optimize the dose, time, and the schedule of the IL-2 treatment. FoxP3 has the potential to assist in evaluating the active process of immunological process, which cannot be evaluated by Th1 and Th2 markers, and FoxP3 can be a successful immunotherapy marker.展开更多
Acute pancreatitis(AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and ...Acute pancreatitis(AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin(IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly antiinflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the antiautophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.展开更多
AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPD...AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain reaction.RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs.CONCLUSION: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.展开更多
Objective To investigate th e anti-tumor effects of GeM10 by the natural killer(NK) cells activities and th e production of Interleukin-2 (IL-2) in peripheral blood mononuclear cells (PB MNCs). Methods Assay of human ...Objective To investigate th e anti-tumor effects of GeM10 by the natural killer(NK) cells activities and th e production of Interleukin-2 (IL-2) in peripheral blood mononuclear cells (PB MNCs). Methods Assay of human NK cells activities by dye reject ion assay in vitro and production of IL-2 in PBMNC by IL-2 bioassay with I L-2 dependent cell line CTLL2 and MTT colorometric method. Results GeM10 could significantly stimulate NK activities (60μg·mL -1 G eM10: 17.077±7.665, 120μg·mL -1 GeM10: 24.9±13.04; control: 7.72±4 .64, P< 0.05). GeM10 could up-regulate the production of IL-2 of PBMNCs in tumor patients(60μg·mL -1 GeM10: 2.965± 1.183; 120μg·mL -1 GeM10: 2.28±0.847; control: 1.792±0.823, P<0.05).Conclu si on The GeM10 not only can stimulate the NK activities but also increase the IL-2 production by PBMNCs in tumor patients. These findings indicate that the GeM10 may have promise as an anti-tumor drug and a biological response modi fier in clinic.展开更多
Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating ...Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LQ20H310002the Scientific Technology Projects of Health and Medicine of Zhejiang Province,No.2020KY308and the Huzhou Science and Technology Fund,No.2020GY39.
文摘BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.
基金Supported by National Natural Science Foundation of China,No.81072692Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.10KJB320007
文摘AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
文摘The capability of recombinant human interleukin-2 ( rhIL-2) and lymphokine-activated killer (LAK) cells in the purging of normal human bone marrows contaminated with human myeloid leukemic cell lines was evaluated. Mixtures of normal human bone marrow mononuclear cells ( BMC) and K562 cells or HL-60 cells (at the BMCK562 ratio of 200:1, 100:1 or 20:1) were incubated with IL-2 with or without LAK cells at the BMC:LAK ratio of 1:1 for one or three days. The nubmers of residual K562 cells, BFU-E and CFU-GM were examined by clonogenic assays. In 200:1 mixture groups without LAK cells, the number of K562 colonies reduced by 50% with no loss of BFU-E and CFU-GM in one-day cultures, and no K562 colonies formed in three-day cultures with about 20% loss of BFU-E and CFU-GM. If the BMC.K562 ratios were 100:1 or 20:1 in the mktures, the leukemic cells could not be eliminated. When the mixtures were incubated with IL-2 and LAK cells, no leukemic cell colonies were detected in the 20:1 group following one-day
文摘Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Method 29 patients with active AS were selected to take GTT (1mg per kg) three times a day for one year. After that, its curative effect was evaluated. The serum level of sIL-2R of these patients was measured by sandwich ELISA method and was compared with that of normal subjects. Result The serum level of sIL-2R in active AS patients was obviously higher than that of the non-active AS patients. (P<0.01). The total effective rate of GTT on AS was 89.6%, while clinical relief rate 27.6%, obvious effective rate 44.8%, effective rate 17.2% and non-effective rate 10.4%. The patients’ serum level of sIL-2R after therapy was significantly lower than that before therapy except patients with no effect. (P<0.05). Conclusion GTT has positive curative effect on active AS patients and could cause obvious decrease of the serum level of sIL-2R. The serum level of sIL-2R can be used as an important index of activity of AS and as a guide of therapy.
文摘INTRODUCTIONMacrophages play an important role in tumor lysisand growth inhibition.They can be activated to atumoricidal state by a variety of agents such asIFNr,TNFα or IL2.The killing machanisms ofactivated macrophages have been extensivelyinvestigated.Recently,it has been proved thatantibody dependent cellular cytotoxicity (ADCC) isone of the potent arms to lyse tumor cells
文摘Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.
基金a grant from the NationalNatural Science Foundation of China (No. 39270658).
文摘Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.
文摘Objective:To investigate the role and the clinical significance of anti-zona pellucidaantibody (AzpAb) and tumor necrosis factor-α(TNF-α),γ-interferon(IFN-γ) and inter-leukin-2 (IL-2) in sera from patients with premature ovarian failure (POF).Methods: The AzpAb in the serum of POF patient was analyzed by means ofELISA. The levels of TNF-α, IL-2 and IFN-γ in the serum were determined by meansof radioimmunoassay (RIA).Results:The level of serum AzpAb in the POF patients was significantly higher thanthat of the normal controls(P＜0.001). The levels of TNF-α and IL-2 were significantlyreduced (P＜0. 001), and the level of IFN-γ was significantly elevated (P＜0.01). Thelevels of above three cytokines in AzpAb positive group were significantly higher thanthose of the negative group in POF patients.Conclusion: This study suggested that AzpAb, TNF-α, IFN-γ and IL-2 might playimportant roles in the pathogenesis of autoimmune POF.
基金Supported by National Natural Science Foundation of ChinaNo.81370576+2 种基金Application Foundation and Advanced Technology Research Plan of TianjinChinaNo.14JCYBJC24800
文摘AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intravenously with Con A at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3(STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein m RNA expression was significantly elevated after IL-22 treatment.CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.
基金Supported by Fondazione Umberto di Mario,Rome,the Broad Medical Research Program Foundation (Grant No. IBD-0154R)and Giuliani SpA,Milan,Italy
文摘In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4+ T helper cells co-expressing interferon-γ and follicular T helper cells.Moreover,both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation.In this article,we review the available data supporting the pathogenic role of IL-21 in IBD.
基金Supported by Key R&D Plan of Science and Technology Department of Jiangxi Province,No.20171BBG70087
文摘BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.
基金Supported by Shandong Provincial Natural Science Foundation,China,No.ZR2012HQ039 and No.ZR2014HP065National Natural Science Foundation of China,No.81373172 and No.81402579
文摘AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin(IL)-24 in hepatocellular carcinoma(HCC) cells.METHODS: γ-secretase inhibitors(GSIs) were used to down-regulate Notch1.Hep G2 and SMMC7721 cells were seeded in 96-well plates and treated with GSI-I or/and IL-24 for 48 h.Cell viability was measured by MTT assay.The cellular and nuclear morphology was observed under a fluorescence microscope.To further verify the apoptotic phenotype,cell cultures were also analyzed by flow cytometry with Annexin V-FITC/propidium iodide staining.The expression of Notch1,SNAIL1,SNAIL2,E-cadherin,IL-24,XIAP and VEGF was detected by Western blot.The invasion and migration capacities of HCC cells were detected by wound healing assays.Notch1 and Snail were downregulated by RNA interference,and the target proteins were analyzed by Western blot.To investigate the mechanism of apoptosis,we analyzed Hep G2 cells treated with si Notch1 or si CON plus IL-24 or not for 48h by caspase-3/7 activity luminescent assay.RESULTS: GSI-I at a dose of 2.5 μmol/L for 24 h caused a reduction in cell viability of about 38% in Hep G2 cells.The addition of 50 ng/m L IL-24 in combination with 1 or 2.5 μmol/L GSI-I reduced cell viability of about 30% and 15%,respectively.Treatment with IL-24 alone did not induce any cytotoxic effect.In SMMC7721 cells with the addition of IL-24 to GSI-I(2.5 μmol/L),the reduction of cell viability was only about 25%.Following GSI-I/IL-24 combined treatment for 6 h,the apoptotic rate of Hep G2 cells was 47.2%,while no significant effect was observed in cells treated with the compounds employed separately.Decreased expression of Notch1 and its associated proteins SNAIL1 and SNAIL2 was detected in Hep G2 cells.Increased E-cadherin protein expression was noted in the presence of IL-24 and GSI-I.Furthermore,the increased GSI-I and IL-24 in Hep G2 cell was associated with downregulation of MMP-2,XIAP and VEGF.In the absence of treatment,Hep G2 cells could migrate into the scratched space in 24 h.With IL-24 or GSI-I treatment,the wound was still open after 24 h.And the distance of the wound closure strongly correlated with the concentrations of IL-24 and GSI-I.Treatment of Notch-1 silenced Hep G2 cells with 50 ng/m L IL-24 alone for 48 h induced cytotoxic effects very similar to those observed in non-silenced cells treated with GSI-I/IL-24 combination.Caspase-3/7 activity was increased in the presence of si Notch1 plus IL-24 treatment.CONCLUSION: Down-regulation of Notch1 by GSI-I or si RNA combined with IL-24 can sensitize apoptosis and decrease the invasion and migration capabilities of Hep G2 cells.
基金Supported by the Shandong Provincial Science and TechnologyCommittee of China,No.2014GGH218034
文摘AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.
基金Supported by National Natural Science Foundation of China,No.81070288 and No.81270452Medical Science and Technology Foundation of Henan Province,No.201001004Science and Technology Leader Overseas Training Foundation of Henan Province,No.201201013
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract,leading to further inflammation.Interleukin(IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells.Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3signaling cascades.This cytokine induces antimicrobial m olecules and proliferative and antiapoptoic pathways,which help prevent tissue damage and aid in its repair.All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity.In this review,we discuss recent progress in the involvement of IL-22in the pathogenesis of IBD,as well as its therapeutic potential.
文摘AIM To investigate interleukin(IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease(IBD) and the function of IL-26. METHODS Human colonic subepithelial myofibroblasts(SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by realtime polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering(si) RNA transfection. RESULTS The m RNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the m RNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and si RNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the m RNA expression of IL-6 and IL-8 induced by IL-26.CONCLUSION These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.
文摘Allergic rhinitis (AR) is the inflammation of nasal mucosa due to the type 1 hypersensitivity reactions mediated by immunoglobulin E (IgE) and triggered by certain allergens. The latest concept in allergic disease is the role of regulatory T cells (Treg). Interleukin-2 enhances the function and survival of Treg to perform its function as a controller of effector for forming a tolerant system by suppressing and regulating the homeostasis system. Treg has a transcription factor FoxP3 which plays a role in developing major function of Treg and progression to produce IL-10 and TGF-?. The atopic diseases are caused by a deficiency of Treg. The new perspective is low-dose IL-2 therapy towards autoimmune disease and allergic inflammation. Low-dose IL-2 therapy requires further clinical studies to optimize the dose, time, and the schedule of the IL-2 treatment. FoxP3 has the potential to assist in evaluating the active process of immunological process, which cannot be evaluated by Th1 and Th2 markers, and FoxP3 can be a successful immunotherapy marker.
文摘Acute pancreatitis(AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin(IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly antiinflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the antiautophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.
基金Supported by the National Natural Science Foundation of China (No.81870643)
文摘AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain reaction.RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs.CONCLUSION: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.
文摘Objective To investigate th e anti-tumor effects of GeM10 by the natural killer(NK) cells activities and th e production of Interleukin-2 (IL-2) in peripheral blood mononuclear cells (PB MNCs). Methods Assay of human NK cells activities by dye reject ion assay in vitro and production of IL-2 in PBMNC by IL-2 bioassay with I L-2 dependent cell line CTLL2 and MTT colorometric method. Results GeM10 could significantly stimulate NK activities (60μg·mL -1 G eM10: 17.077±7.665, 120μg·mL -1 GeM10: 24.9±13.04; control: 7.72±4 .64, P< 0.05). GeM10 could up-regulate the production of IL-2 of PBMNCs in tumor patients(60μg·mL -1 GeM10: 2.965± 1.183; 120μg·mL -1 GeM10: 2.28±0.847; control: 1.792±0.823, P<0.05).Conclu si on The GeM10 not only can stimulate the NK activities but also increase the IL-2 production by PBMNCs in tumor patients. These findings indicate that the GeM10 may have promise as an anti-tumor drug and a biological response modi fier in clinic.
基金support for this work for ASH was from National Eye Institute R01 EY026546an NEI Center Core Grant EY014801.
文摘Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.
