European cytokine network最新文献

{"title":"Toll-like receptors pathway in common variable immune deficiency (CVID) and X-linked agammaglobulinemia (XLA).","authors":"Parsova Tavasolian,&nbsp;Laleh Sharifi,&nbsp;Asghar Aghamohammadi,&nbsp;Farshid Noorbakhsh,&nbsp;Rouzbeh Sanaei,&nbsp;Mahsima Shabani,&nbsp;Nima Rezaei","doi":"10.1684/ecn.2018.0420","DOIUrl":"https://doi.org/10.1684/ecn.2018.0420","url":null,"abstract":"<p><p>Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are two major humoral immunodeficiencies, causing a high rate of early age mortality in children. In order to identifiy the possible factors involved in the pathogenesis of CVID and XLA, recent studies have focused on Toll-like receptors (TLRs) and demonstrate the defects in different TLR pathways in immune cells of CVID and XLA patients. Herein, we measured TLR-4 and TLR-9 RNA levels and consequently TNF-α and IFN-α production in peripheral blood mononuclear cells (PBMCs) of patients with CVID and XLA. Contrary to healthy individuals, TLR-9 expression was not significantly increased after ligand stimulation, whereas ligand-induced TLR-4 expression was not significantly different from that in healthy control PBMCs. Lipopolysaccharide (LPS)-stimulated TNF-α production was significantly reduced in patients compared to controls, whereas IFN-α production was increased in all groups after CpG stimulation without any significant inter-group difference. Our data suggest that defects in TLR-9 activated pathways may be a result of the decreased TLR-9 expression, although TLR-9 is not the only modulator of IFN-α production in these patients. On the other hand, impaired signaling in TLR-4 activated pathways which results in significant reduction in TNF-α production are not related to a defect in TLR-4 expression.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 4","pages":"153-158"},"PeriodicalIF":2.8,"publicationDate":"2018-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36901013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine and molecular networks in sepsis cases: a network biology approach.","authors":"Dong Wook Jekarl,&nbsp;Kyung Soo Kim,&nbsp;Seungok Lee,&nbsp;Myungshin Kim,&nbsp;Yonggoo Kim","doi":"10.1684/ecn.2018.0414","DOIUrl":"https://doi.org/10.1684/ecn.2018.0414","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition of organ dysfunction caused by a dysregulated host immune response to infection. We performed network analysis of cytokine molecules and compared network structures between a systematic inflammatory response syndrome (SIRS) or normal control (NC) group and a sepsis group. We recruited SIRS (n = 33) and sepsis (n = 89) patients from electronic medical records (EMR) according to whether data on PCT, CRP, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17, IL-22, TNF-α, and IFN-γ levels were available. From the public GEO dataset, GSE66099, GSE9960, GSE95233, GSE57065 were downloaded. Genes corresponding to 15 molecules were extracted from an expression array. A correlation matrix was formed for the 15 molecules and statistically significant molecular pairs were used as pairs for network analysis of coexpression. The number of molecular or gene expression pairs significantly correlated among the SIRS or control and sepsis groups are as follows for datasets: EMR, 15 and 15; GEO66099-1, 13 and 15; GEO9960, 13 and 11; GSE95233, 13 and 8; GSE66099-2, 15 and 14; GSE57065, 14 and 13, respectively. Network analysis revealed that network diameter, number of nodes and shortest path were equal to or lower in the sepsis group. The coexpression network in sepsis patients was relatively small sized and had lower shortest paths compared with the SIRS group or healthy control group. Cytokines with one degree (k = 1) are increased in sepsis group compared with SIRS or healthy control group. IL-9 and IL-2 were not included in network of sepsis group indicating that these cytokines showed no correlation with other cytokines. These data might imply that cytokines tend to be dysregulated in the sepsis group compared to that of SIRS or normal control groups.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 3","pages":"103-111"},"PeriodicalIF":2.8,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36825392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines and male infertility.","authors":"Vassiliki Syriou,&nbsp;Dimitrios Papanikolaou,&nbsp;Ariadni Kozyraki,&nbsp;Dimitrios G Goulis","doi":"10.1684/ecn.2018.0412","DOIUrl":"https://doi.org/10.1684/ecn.2018.0412","url":null,"abstract":"<p><p>Many male infertility cases have no apparent cause, being characterized as idiopathic. Both inflammation and obesity have long been associated with infertility. On one hand, inflammation, such as orchitis and male accessory gland infections (MAGIs), are regulated by inflammatory cytokines. The latter are also produced in the testis by Leydig and Sertoli cells, being associated with gap junctional communication at the blood-testis barrier. Furthermore, they regulate spermatogenesis through cell interaction, Toll-like receptors and production of reactive oxygen species. Additionally, they affect testosterone production, acting at many levels of the pituitary - gonadal axis. Any imbalance in their production may result in infertility. On the other hand, obesity has also been associated with infertility. Adipokines, cytokines produced by white adipose tissue, regulate the lipid and glucose metabolism and the inflammatory system. Recent data on leptin show that it regulates reproduction by adjusting hypothalamus - pituitary - gonadal axis at both the central and peripheral levels. In this regard, resistin, visfatin and the GH secretagogue peptic hormone ghrelin affect spermatogenesis, whereas data on adiponectin are rather scarce. In conclusion, inflammatory cytokines and adipokines seem to have a pivotal role in the regulation of spermatogenesis; any imbalance in this stable environment may lead to infertility. Nevertheless, further studies are needed to clarify their exact role.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 3","pages":"73-82"},"PeriodicalIF":2.8,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36825394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased IL-1β levels are associated with an imbalance of \"oxidant/antioxidant\" status during Behçet's disease.","authors":"Arezki Chekaoui,&nbsp;Karima Lahmar,&nbsp;Houda Belguendouz,&nbsp;Fettoum Mazari,&nbsp;Malika Terahi,&nbsp;Djenette Hakem,&nbsp;Pierre Youinou,&nbsp;Chafia Touil-Boukoffa","doi":"10.1684/ecn.2018.0411","DOIUrl":"https://doi.org/10.1684/ecn.2018.0411","url":null,"abstract":"<p><p>Behçet's disease is a multisystem disease. It stands at the crossroad between the autoimmunity and auto-inflammatory disorders. In this study, we sought to address a relationship that might exist between interleukin-1β (IL-1β) and the oxidants/antioxidants markers in Behçet's patients. Behçet's disease patients (n = 78: active stage, n = 28; inactive stage, n = 50) and 41 healthy controls have been included in our study. In this context, we investigated the plasma levels of IL-1β and the nitrosative/oxidative markers: nitric oxide (NO), advanced oxidative protein products (AOPP) and fatty acids peroxidation-malondialdehyde (MDA). The antioxidant system was assessed by measuring the plasma level of superoxide dismutase (SOD) activity. The Mann-Whitney's U and Pearson's correlation tests were used for statistical analyses. Our case-control study showed that patients in active stage displayed higher plasma levels of IL-1β, NO, AOPP and MDA versus healthy controls and patients in inactive stage. Patients in active stage showed significantly lower SOD levels related to patients in inactive stage and healthy controls respectively, whereas patients in inactive stage showed statistically insignificant SOD level versus healthy controls. Correlation studies showed a significant positive correlation between IL-1β and AOPP, IL-1β and NO, and negative correlation between IL-1β and SOD among Behçet's disease patients. In addition, we showed positive correlation between AOPP and NO, AOPP and MDA and negative correlation between NO and SOD, AOPP and SOD in Behçet's disease patients. Interestingly, our study revealed that IL-1β levels increased and correlated with an imbalance of oxidants/antioxidants system, especially during active stage of Behçet disease. Collectively, our study indicates a possible link between IL-1β production and nitrosative/oxidative markers during Behçet's disease. Exploiting this relationship might provide valuable outputs in the follow-up and prognosis of Behçet's disease with a potential therapeutic value.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 3","pages":"95-102"},"PeriodicalIF":2.8,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36825396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated adiponectin and sTNFRII serum levels can predict progression to hepatocellular carcinoma in patients with compensated HCV1 cirrhosis.","authors":"Jean-Philippe Bastard,&nbsp;Soraya Fellahi,&nbsp;Étienne Audureau,&nbsp;Richard Layese,&nbsp;Françoise Roudot-Thoraval,&nbsp;Carole Cagnot,&nbsp;Valérie Mahuas-Bourcier,&nbsp;Angela Sutton,&nbsp;Marianne Ziol,&nbsp;Jacqueline Capeau,&nbsp;Pierre Nahon","doi":"10.1684/ecn.2018.0413","DOIUrl":"https://doi.org/10.1684/ecn.2018.0413","url":null,"abstract":"<p><p>An obesity-related altered adipose tissue secretion is suggested as a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) cirrhosis. However, no prospective study has yet examined the predictive value of circulating adipokines and immuno-inflammatory biomarkers regarding this risk. This was a case-control study nested in a prospective French national cohort of HCV-infected patients with biopsy-proven compensated cirrhosis. We selected 56 HCV1-infected patients who subsequently developed HCC (cases), and 96 controls matched for age, gender and diabetes, not developing HCC after a similar period. Adipokines and immuno-inflammatory biomarkers were determined on baseline frozen serum samples. Their influence on the occurrence of HCC was assessed using a mixed logistic regression model under univariate analysis and a backward stepwise procedure under multivariate analysis. The patients were mostly male (62.5%) with active HCV replication (83%) and had been followed for a median duration of 6.3 years during which 44.4% achieved a sustained viral response. Higher adiponectinemia levels were found in cases than in controls (P = 0.01). Levels of the immuno-inflammatory markers were similar in both groups except sTNFRII >5,000 pg/mL (52% cases versus 24% controls; P = 0.001). No marker was associated with histological steatosis. Under multivariate analysis, baseline adiponectin and sTNFRII levels were independently associated with the occurrence of HCC, alongside previous excessive alcohol intake and HCV viral load. High baseline circulating adiponectin and sTNFRII levels were associated with an increased risk of HCC in patients with HCV1 cirrhosis, independently of their HCV replication status.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 3","pages":"112-120"},"PeriodicalIF":2.8,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36825393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity and inflammation.","authors":"Jacek Karczewski,&nbsp;Ewelina Śledzińska,&nbsp;Alina Baturo,&nbsp;Izabela Jończyk,&nbsp;Aleksander Maleszko,&nbsp;Paweł Samborski,&nbsp;Beata Begier-Krasińska,&nbsp;Agnieszka Dobrowolska","doi":"10.1684/ecn.2018.0415","DOIUrl":"https://doi.org/10.1684/ecn.2018.0415","url":null,"abstract":"<p><p>The prevalence of obesity has recently increased dramatically and has contributed to the increasing prevalence of various pathological conditions, including type 2 diabetes mellitus, nonalcoholic fatty liver disease, asthma, various types of cancer, cardiovascular and neurodegenerative diseases, and others. Accumulating evidence points to localized inflammation in adipose tissue, which, in turn, promotes systemic low-grade inflammation as a primary force contributing to the development of these pathologies. A better understanding of the underlying mechanisms behind obesity-induced adipose tissue inflammation is required to develop effective therapeutic or prophylactic strategies. This review is aimed to present the current knowledge of adipose tissue inflammation associated with obesity.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 3","pages":"83-94"},"PeriodicalIF":2.8,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36825395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance of serum leptin level in patients with gastric cancer.","authors":"Faruk Tas,&nbsp;Senem Karabulut,&nbsp;Kayhan Erturk,&nbsp;Derya Duranyildiz","doi":"10.1684/ecn.2018.0408","DOIUrl":"https://doi.org/10.1684/ecn.2018.0408","url":null,"abstract":"<p><p>Leptin may support the proliferation and hinder the apoptosis of tumor cells. Although leptin expression has been studied in several human tumors, its potential clinical significance remains uncertain in patients with gastric carcinoma. Furthermore, the majority of available findings have been determined from preclinical studies using stomach carcinoma tissue section and, to date, few studies have evaluated the clinical significance of leptin in the serum or plasma of gastric carcinoma patients. In the current study, the serum concentration of soluble leptin was assessed in gastric carcinoma patients, and its contributions to the clinical parameters and prognosis of patients were determined. A total of 63 pathologically confirmed gastric cancer patients and 30 healthy subjects were enrolled in the study and circulating leptin levels in the serum of all subjects were determined by ELISA. The serum leptin concentrations were significantly lower in the gastric cancer patients compared with the healthy control group (P = 0.009). In the gastric cancer patients, the clinical features of patient age, sex, lesion localization, histopathology, pathological grade, stage of disease, and serum tumor markers including lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 19-9 were not correlated with serum leptin concentration. Furthermore, no association was observed between serum leptin concentration and responsiveness to chemotherapy (P = 0.51), and leptin level had no apparent prognostic role in clinical outcome (P = 0.57). In conclusion, although it was not predictive or prognostic, serum leptin level may be a valuable diagnostic indicator in patients with gastric carcinoma.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 2","pages":"52-58"},"PeriodicalIF":2.8,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36370894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of new anti-IL-6 antibodies revealed high potency candidates for intracellular cytokine detection and specific targeting of IL-6 receptor binding sites.","authors":"Karinna Chouman,&nbsp;Birgit Korioth-Schmitz,&nbsp;Markus Sack,&nbsp;Jörn Engelbert Schmitz,&nbsp;Anh Tuan Pham,&nbsp;Rainer Fischer,&nbsp;Stefan Barth,&nbsp;Torsten Klockenbring,&nbsp;Rolf Fendel","doi":"10.1684/ecn.2018.0409","DOIUrl":"https://doi.org/10.1684/ecn.2018.0409","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) expression and secretion, induced by inflammatory processes, stimulate the acute phase response cascade. The overexpression of IL-6 contributes to a variety of inflammatory diseases, e.g. rheumatoid arthritis, Castleman's disease, multiple myeloma, and prostate cancer. Screening for high amounts of IL-6 in the patients' blood serum can be crucial for an adequate treatment. In this study, five novel murine monoclonal antibodies (mAbs) reactive to human IL-6 were generated. The mAbs were characterized for potential diagnostic purposes and recombinant antibodies were derived thereof. Initial epitope mapping using a combination of blocking experiments and Hyper-IL-6, a fusion protein consisting of IL-6 and the soluble IL-6 receptor revealed distinct but overlapping binding sites. At least one of the mAbs was found to interact with the region of IL-6/ IL-R complex formation. Three mAbs were applied successfully in intracellular staining by flow cytometry, whereas one of the mAbs showed comparable binding as a reference reagent. Furthermore, the mAbs were tested for applications in various immunological assays such as ELISA, Western blot and surface plasmon resonance spectroscopy (SPR), using IL-6 from commercial sources as well as in-house produced protein (IL-6_IME). The limit of detection was determined by sandwich ELISA (0.5 ng/mL, SD ±0.005). Our results also demonstrated that the recombinant IL-6 produced was functional and correctly folded. These findings support the use of the generated mAb clones as promising candidates for application in various immunological assays for diagnostic and scientific purposes.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 2","pages":"59-72"},"PeriodicalIF":2.8,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36432447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of IL-18 in transplant biology.","authors":"Chen Liu,&nbsp;Juntao Chen,&nbsp;Baoqing Liu,&nbsp;Shunzong Yuan,&nbsp;Dawei Shou,&nbsp;Liang Wen,&nbsp;Xiaoying Wu,&nbsp;Weihua Gong","doi":"10.1684/ecn.2018.0410","DOIUrl":"https://doi.org/10.1684/ecn.2018.0410","url":null,"abstract":"<p><p>Since pro-inflammatory cytokine IL-18 and its receptor (IL-18R) are closely involved in regulating both adaptive and innate immune responses, it is conceivable that they might play an important role in organ transplantation. IL-18 can stimulate lymphocytes to produce the IFN-γ and regulate macrophage activity, thereby increasing the expression of proinflammatory cytokines including IL-1β, IL-6, CCL4 (macrophage inflammatory protein-1 β), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1). Nevertheless, the IL-18 signaling pathway and its underlying mechanisms remain obscure in transplant biology. This review is to summarize recent advances in our knowledge about the IL-18 signaling pathway and to analyze their functions in transplant-related biology. It was found that IL-18/IL-18R signaling pathway contributed to vascular transplantation, ischemmia/reperfusion, acute kidney injury, and acute rejection of kidney/liver/heart transplantation. IL-18 was a potential CYP3A expression modulator and was capable of affecting tacrolimus pharmacokinetics. Neutralizing IL-18 by its inhibitor IL-18 binding protein could efficiently suppress the production of injury-associated cytokines such as IL-6, TNF-α, IFN-γ, CXCL10 (IFN-γ-inducible protein10), and CX₃CL1 (fractalkine) and improve allograft function. Blockade of IL-18 signaling could regulate cardiomyocyte apoptosis and inhibit Th17 cells differentiation. Alteration of IL-18 levels was suggested as a biomarker for predicting ongoing allograft outcome. All these activities could deepen our understanding of immunobiological role of IL-18 and its receptor in the field of organ transplantation. Intervention of IL-18 signaling pathway might be utilized as a therapeutic strategy in clinic.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 2","pages":"48-51"},"PeriodicalIF":2.8,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36372657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis.","authors":"Mahmoud Al-Azab,&nbsp;Jing Wei,&nbsp;Xunli Ouyang,&nbsp;Abdalkhalig Elkhider,&nbsp;Williams Walana,&nbsp;Xiaotong Sun,&nbsp;Yawei Tang,&nbsp;Bing Wang,&nbsp;Xia Li","doi":"10.1684/ecn.2018.0405","DOIUrl":"https://doi.org/10.1684/ecn.2018.0405","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2). We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients' samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"29 1","pages":"27-35"},"PeriodicalIF":2.8,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2018.0405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36087612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}