Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

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.

Drug-induced entero-colitis due to interleukin-17 inhibitor use;capsule endoscopic findings and pathological characteristics:A case report

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.

Role of IL-17 in nucleus pulposus cell proliferation and metabolism cultured in vitro

Objective:To explore the role of cytokine,interleukin-17(IL-17) in human degenerative dise disease.Methods:Through magnetic resonance imaging.human degenerative disc tissues were confirmed from the isolated nucleus pulposus cells.which were then cultured in vitro.The cells were cultured with and without different concentrations of IL-17.2 ng/mL,5 ng/mL.10 ng/mL.15 ng/mL.and 20 ng/mL.IL-17 cuncentrations were uses for stimulalion.After 72 hours,the inhibition rate of proliferation was measured by MTS method.For 48 and 96 hours,the nucleus pulposus cells were cultured with and without the appropriate IL-17 concentrations.The mRNA and protein expression levels of the matrix macromoleeules and degrading tissue genes were measured by Real-time PCR and Western blot analysis.Results:It was noted that nucleus pulposus cell proliferation was inhibited alter culturing in vitro with IL-17 stimulation.and it was further observed that the inhibition effect was significantly stronger with 15 ng/ml.IL-17 concentration.With the dosage of 15 ng/mL.IL-17 stimulation induced multiple cellular responses.such as the significant increase in mRNA expression for both aggrecan(ACAN) and type Ⅰ collagen(COLIa1) genes(P<0.05).and the significant decrease in mRNA expression of both degrading tissue genes.MMP3 and TI.MP3(P<0.05).Western blot results also showed that the protein level ol COLIA1 was significantly decreased t=3.199.P=0.006).while the protein level ol one peptidases(ADAMTS5) significantly increased(t=2.667.P=0.021).Conclusions:These findings suggest that IL-17 can inhibit proliferation and affect the metabolism ol the cultured nucleus pulposus cells in vitro,and these findings could possibly contribute to the degenerative changes that occur in DDD through extracellular matrix synthesis inhibition,promoting nucleus pulposus extracellular matrix degradation and disrupting the metabolic balance.

Association between Metabolic Syndrome Components and Serum High-Sensitivity C-Reactive Protein or Interleukin-6 Levels among Congolese Adults

Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of our study was to address the association between MetS components with serum hs-CRP and IL-6 levels among Congolese adults. A total of 357 participants (aged 30 - 87 years) were included in this cross-sectional study. Anthropometrics were collected and fasting blood sampled for assessment of fasting blood glycaemia (FBG), lipids and inflammatory parameters using commercially available assays. NCEP-ATPIII criteria were used to define MetS. The Median (IQR) hs-CRP and IL-6 levels were higher in participants with MetS than in those without ([7 (4, 14) versus 6 (4, 8)] mg/L;p = 0.092 and [23.8 (20.9, 27.6) versus 22.3 (19.5, 25.0)] pg/mL;p = 0.002). hs-CRP and IL-6 levels were significantly higher in females with MetS than in those without, but not in males. Among participants, only TG was correlated with hs-CRP (r = 0.149, p = 0.007), and a significant correlation was observed between TG (r = 0.116, p = 0.037), FBG (r = 0.208, p = 0.000), HDL-C (r = −0.119, p = 0.034) and SBP (r = 0.143, p = 0.010) and IL-6. In males, hs-CRP levels were positively correlated with TG (0.316;p = 0.000), negatively with HDL-C (r = −0.290, p = 0.0022), without such correlations in females. In Ames, IL-6 levels were positively correlated with FBG (r = 0.202;p = 0.035), and negatively with HDL-C (r = −0.249, p = 0.009). Significant correlations between IL-6 levels and FBG (r = 0.214;p = 0.000) or SBP (r = 0.227, p = 0.000) were observed in females. Logistic regression analysis was carried out to identify the relationship between MetS components and hs-CRP or IL-6. Values of area under receiver-operating characteristic (ROC) curves suggest potential use of serum hs-CRP (AUC = 0.675) and IL-6 (AUC = 0.656) as diagnostic biomarkers of MetS. Combination of hs-CRP and IL-6 improved diagnosis accuracy, yielding a 0.698 ROC curve area. MetS components are associated with hs-CRP and IL-6 levels among adults Congolese. Combining the two biomarkers hs-CRP and IL-6 improves Mets diagnostic accuracy compared to hs-CRP or IL-6 alone.

铜代谢相关基因COX17与头颈部鳞状细胞癌不良预后相关

目的:探讨铜代谢相关基因细胞色素c氧化酶铜伴侣17(COX17)对头颈部鳞状细胞癌(HNSCC)发生发展及预后的影响。方法:运用生物信息学分析COX17在HNSCC与正常组织中的表达差异;通过构建列线图验证COX17在预测HNSCC预后中的作用;采用KEGG和GO分析对COX17相关基因进行功能富集分析以及利用ssGSEA分析COX17表达与HNSCC组织中免疫细胞浸润丰度的关系;采用实时定量聚合酶链反应(RT-qPCR)验证COX17在HNSCC细胞系与永生化正常上皮细胞系中的表达差异;细胞活力试剂盒(CCK-8)和Transwell实验分别用于检测COX17对细胞增殖、侵袭能力的影响。结果:COX17在HNSCC中表达显著上调(P<0.05)。预后分析表明COX17与HNSCC患者总生存期(OS)密切相关(P<0.05)。免疫浸润相关性分析显示,COX17与多种免疫细胞浸润丰度呈负相关关系(均P<0.001)。敲低COX17可显著抑制HNSCC细胞SCC-9、SAS细胞的增殖及侵袭能力。结论:COX17的表达可影响HNSCC细胞的增殖和侵袭,并与HNSCC组织中免疫细胞浸润存在潜在关联;作为线粒体铜代谢分子标记物,COX17可能是评估HNSCC预后的有效指标和潜在治疗靶点。

右美托咪定对全弓置换术患者脑氧代谢及外周血Th17/Treg细胞亚群的影响

目的探讨右美托咪定对全弓置换术患者脑氧代谢及外周血Th17/Treg细胞亚群的影响。方法92例全弓置换术患者随机分为对照组(46例)和观察组(46例),对照组给与常规麻醉诱导,观察组在常规麻醉诱导的基础上给予右美托咪定。观察两组麻醉诱导前(t_(0))、手术结束即刻(t_(1))、手术后12 h(t_(2))脑氧代谢、中枢神经特异性蛋白(S100β蛋白)和神经元特异性烯醇化酶(NSE)水平、外周血Th17和Treg细胞亚群及相关炎性细胞因子水平。结果观察组t_(1)和t_(2)时点SjvO2水平显著高于对照组(P<0.05),而AVDO2和CERO2水平显著低于对照组(P<0.05);观察组t_(2)时点S100β和NSE水平显著低于对照组(P<0.05);观察组t_(2)时点外周血Th17细胞和Th17/Treg比值水平显著低于对照组(P<0.05),而t_(2)时点外周血Treg细胞水平显著高于对照组(P<0.05);观察组t_(2)时点外周血IL-17水平显著低于对照组(P<0.05),而外周血TGF-β水平显著高于对照组(P<0.05)。结论右美托咪定能改善全弓置换术患者脑氧代谢及外周血Th17和Treg细胞亚群的失衡程度,从而起到脑保护的作用。

Interleukin-17 plays a critical role in the acute rejection of intestinal transplantation

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.

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A metaanalysis

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.

Polymorphism in the interleukin-17A promoter contributes to gastric cancer

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.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

Expression of Interleukin-17 in Lung and Peripheral Blood of Asthmatic Rats and the Influence of Dexamethasone

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.

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

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.

Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression

BACKGROUND Ulcerative colitis(UC)is a chronic disease characterized by inflammation of intestinal epithelium,primarily of the colon.An increasing prevalence of metabolic syndrome(MetS)in patients with UC has been documented recently.Still,there is no evidence that MetS alters the course of the UC.AIM To test the influence of the MetS on the severity of UC and the local and systemic immune status.METHODS Eighty nine patients with de novo histologically confirmed UC were divided in two groups,according to ATP III criteria:Group without MetS(no MetS)and group with MetS.RESULTS Clinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin-10(IL-10)and fecal content of Galectin-3(Gal-3)was observed in subjects with UC and MetS,compared to subjects suffering from UC only.This was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factorα(TNF-α),interleukin-6(IL-6),and interleukin-17(IL-17)in the sera as well as Gal-3 over TNF-αand IL-17 in feces of UC patients with MetS.Further,the patients with both conditions(UC and MetS)had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina propria.CONCLUSION Local dominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.

Unexpected alliance between syndecan-1 and innatelike T cells to protect host from autoimmune effects of interleukin-17

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.

Suppressive effect of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on inflammation by regulation of NF-κB pathway and interleukin-17 in mice with dextran sulphatesodium-induced ulcerative colitis

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.

Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation

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.

Interleukin-17A gene variants and risk of coronary artery disease:a large angiography-based study

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.

Interleukin-17 mediates liver progenitor cell transformation into cancer stem cells through downregulation of miR-122

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.

Syndecan-1-coating of interleukin-17-producing natural killer T cells provides a specific method for their visualization and analysis

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.

骨质疏松患者Th17/Treg细胞平衡状况及其与骨代谢指标的相关性

目的研究骨质疏松患者辅助性T细胞17(Th17)、调节性T细胞(Treg)细胞平衡状况及其与骨代谢指标的相关性。方法回顾性分析2019年3月至2022年2月在宝鸡市妇幼保健院诊治的120例骨质疏松患者(骨质疏松组)的临床资料,另选择同期在我院体检的100例健康者作为对照组。比较两组受检者的Th17、Treg、骨代谢炎性细胞因子指标[包括肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)、转化生长因子-β(TGF-β)]及骨代谢蛋白酶活性指标[包括基质金属蛋白酶-2(MMP-2)、Ⅰ型胶原吡啶交联终肽(ICTP)、Ⅰ型前胶原氨基端原肽(PINP)]水平,采用Spearman相关性分析Th17、Treg与骨代谢指标的相关性。结果骨质疏松组患者的Th17水平为(2.30±0.41)%,明显高于对照组的(1.43±0.35)%,Treg水平为(3.18±0.78)%,明显低于对照组的(4.47±0.63)%,差异均有统计学意义(P<0.05);骨质疏松组患者的TNF-α、IL-6水平分别为(7.63±1.05)ng/mL、(33.60±5.35)pg/mL,明显高于对照组的(3.36±0.47)ng/mL、(20.34±3.28)pg/mL,IL-10、TGF-β水平分别为(16.61±2.19)pg/mL、(21.39±6.11)pg/mL,明显低于对照组的(29.51±3.55)pg/mL、(40.47±10.35)pg/mL,差异均有统计学意义(P<0.05);骨质疏松组患者的MMP-2、ICTP水平分别为(912.36±109.82)ng/mL、(6.50±0.84)ng/mL,明显高于对照组的(648.59±75.28)ng/mL、(4.02±0.56)ng/mL,PINP水平为(0.85±0.13)ng/mL,明显低于对照组的(1.44±0.20)ng/mL,差异均有统计学意义(P<0.05);经Spearman分析结果显示,Th17与TNF-α、MMP-2、ICTP呈正相关(P<0.05),Treg与TNF-α、MMP-2、ICTP呈负相关(P<0.05),与TGF-β呈正相关(P<0.05)。结论骨质疏松患者中Th17水平提升、Treg表达水平降低,它们共同干扰骨代谢期间的炎性反应与蛋白酶活性。