Chuanjun Huang, Yan Sun, Na Liu, Ziping Zhang, Xiyan Wang, Degan Lu, Ling Zhou, Caiqing Zhang
{"title":"IL-27 attenuates airway inflammation and epithelial-mesenchymal transition in allergic asthmatic mice possibly via the RhoA/ROCK signalling pathway","authors":"Chuanjun Huang, Yan Sun, Na Liu, Ziping Zhang, Xiyan Wang, Degan Lu, Ling Zhou, Caiqing Zhang","doi":"10.1684/ecn.2021.0476","DOIUrl":"https://doi.org/10.1684/ecn.2021.0476","url":null,"abstract":"<p><strong>Background: </strong>Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-β1-induced EMT in 16HBE cells in vitro.</p><p><strong>Methods: </strong>Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT.</p><p><strong>Results: </strong>Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-β1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA.</p><p><strong>Conclusion: </strong>Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 1","pages":"13-24"},"PeriodicalIF":2.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354500","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}
Jacek Karczewski, Aleksandra Zielińska, Rafał Staszewski, Piotr Eder, Agnieszka Dobrowolska
{"title":"Metabolic link between obesity and autoimmune diseases.","authors":"Jacek Karczewski, Aleksandra Zielińska, Rafał Staszewski, Piotr Eder, Agnieszka Dobrowolska","doi":"10.1684/ecn.2021.0474","DOIUrl":"https://doi.org/10.1684/ecn.2021.0474","url":null,"abstract":"<p><p>The abnormal accumulation of visceral adipose tissue in obesity is associated with metabolic changes that include altered glucose tolerance, insulin resistance, hyperlipidemia, and metabolic syndrome. Obesity also coincides with increased incidence of autoimmune diseases. Accumulating evidence suggest that prolonged metabolic overload related to overnutrition, influenced by genetic and epigenetic factors, might affect immunologic self-tolerance through changes in the energy metabolism of immune cells, particularly regulatory T (Treg) cells. A strong activation of nutrient-energy signaling pathways blocks the induction of the transcription factor forkhead P3 (FOXP3), a master regulator of Treg cells, consequently inhibiting their generation and proliferation, thereby promoting proinflammatory response. Expanding our knowledge on the topic, particularly on metabolic T cell flexibility in vivo will provide new insights that can be used to develop therapeutic strategies for various inflammatory diseases, including obesity and autoimmune diseases. Targeting specific metabolic pathways is emerging as an important approach to control immune response and maintain immunological homeostasis.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 4","pages":"64-72"},"PeriodicalIF":2.8,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39888557","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}
Sara Ibrahim Taha, Sara Farid Samaan, Rehab Ali Ibrahim, Eman Mousa El-Sehsah, Mariam Karam Youssef
{"title":"Post-COVID-19 arthritis: is it hyperinflammation or autoimmunity?","authors":"Sara Ibrahim Taha, Sara Farid Samaan, Rehab Ali Ibrahim, Eman Mousa El-Sehsah, Mariam Karam Youssef","doi":"10.1684/ecn.2021.0471","DOIUrl":"https://doi.org/10.1684/ecn.2021.0471","url":null,"abstract":"<p><strong>Background: </strong> Various musculoskeletal and autoimmune manifestations have been described in patients with coronavirus disease 2019 (COVID-19). Objectives: This study aims to investigate the prevalence and etiology of arthritis in post-COVID Egyptian patients. Methods: We included 100 post-COVID Egyptian patients who recovered 6 months ago and assessed several inflammatory and autoimmune markers. Results: The prevalence of post-COVID arthritis was 37%. Ankle, knee, and wrist were the most commonly affected joints. Old age (P = 0.010), smoking (P = 0.001), and arthralgia (P = 0.049) were all linked with post-COVID arthritis. Levels of pretreatment (baseline) interleukin (IL)-6 (46.41 ± 3.67 vs. 24.03 ± 2.46; P = 0.001), as well as 6-month post-COVID C-reactive protein (CRP; 98.49 ± 67.55 vs. 54.32 ± 65.73; P = 0.002), and erythrocyte sedimentation rate (ESR; 109.08 ± 174.91 vs. 58.35 ± 37.87; P = 0.029) were significantly higher in patients with arthritis compared to those without. On the other hand, complement C3 (P = 0.558) and C4 (P = 0.192), anti-nuclear antibodies (P = 0.709), and anti-cyclic citrullinated peptides (anti-CCP; P = 0.855) did not show significant differences. Only pretreatment IL-6 level was the significant single predictor of post-COVID arthritis with an odds ratio (95% confidence interval) of 3.988 (1.460-10.892) and a P-value of 0.007.</p><p><strong>Conclusion: </strong> The strong association observed with inflammatory markers (ESR and CRP) and the insignificant association with serologic markers of autoimmunity (ANA and anti-CCP) in our study support the notion that the underlying mechanism of post-COVID-19 arthritis is primarily due to the hyperinflammatory process associated with COVID-19 infection, and not the result of an autoimmune reaction. IL-6 levels before therapy can predict post-COVID arthritis allowing for early management.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 4","pages":"83-88"},"PeriodicalIF":2.8,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39888558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuancong Jiang, Deqiang Kong, Xiaolong Miao, Xing Yu, Zelai Wu, Han Liu, Weihua Gong
{"title":"Anti-cytokine therapy and small molecule agents for the treatment of inflammatory bowel disease.","authors":"Yuancong Jiang, Deqiang Kong, Xiaolong Miao, Xing Yu, Zelai Wu, Han Liu, Weihua Gong","doi":"10.1684/ecn.2021.0472","DOIUrl":"https://doi.org/10.1684/ecn.2021.0472","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, with multifactorial etiologies has led to a global health-associated burden in many countries. Substantial efforts are devoted to understand the pathogenesis, behavioral and environmental triggers, which may be specifically valuable for the treatment of IBD. The specific pathogenesis underlying IBD is as yet incompletely understood. The use of anti-cytokine therapy and small molecule agents targeting the immune system is thought to restore the body's intestinal barrier function and relieve inflammation with manageable adverse effects. In this review, we report recent advances in anti-cytokine therapy and treatment with small molecule agents for the management of IBD.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 4","pages":"73-82"},"PeriodicalIF":2.8,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39888556","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}
Mahsa Keshavarz-Fathi, G. Sanati, M. Sadr, Bahareh Mohebbi, V. Ziaee, N. Rezaei
{"title":"Aberrant DNA methylation of the promoters of JAK2 and SOCS3 in juvenile systemic lupus erythematosus","authors":"Mahsa Keshavarz-Fathi, G. Sanati, M. Sadr, Bahareh Mohebbi, V. Ziaee, N. Rezaei","doi":"10.1684/ecn.2021.0469","DOIUrl":"https://doi.org/10.1684/ecn.2021.0469","url":null,"abstract":"Cytokine dysregulation is one of the important hallmarks of systemic lupus erythematosus (SLE) in both pediatric and adult patients. Owing to the substantial role of Janus kinase (JAK) and suppressor of cytokine signaling (SOCS) in cytokine signaling, we compared the methylation status of the promoter of JAK2 and SOCS3 between patients with JSLE and healthy controls. Peripheral blood samples were obtained from patients with JSLE and healthy controls. The promoter methylation was assessed by using the bisulfite conversion system and real-time quantitative multiplex methylation-specific PCR (QM-MSP). The methylation assessments were performed on the blood samples of 25 patients with JSLE and 24 healthy controls. The promoter of JAK2 was significantly hypomethylated in patients with JSLE compared to healthy controls. The median relative unmethylation of the promoter of JAK2 was higher in the JSLE group compared to the control group [0.44 (0.32,0.59) vs. 0.18 (0.12,0.86), respectively; P-value 0.026]. The promoter of SOCS3 was significantly hypermethylated in patients with JSLE compared to the controls. The median relative unmethylation of the promoter of SOCS3 was lower in the JSLE group compared to the control group [0.52 (0.10, 1.41) vs 1.18 (0.39, 2.19), respectively; P-value 0.032]. According to the results of our study, hypomethylation of the promoter of JAK2 and hypermethylation of the promoter of SOCS3 associate with JSLE. These alterations are possible mechanisms for activation of the JAK2 and suppression of the SOCS3 gene, respectively.","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 1","pages":"48 - 54"},"PeriodicalIF":2.8,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47428967","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}
S. Baioumy, D. Sallam, S. Abdalgeleel, S. Fouad, Ahmed S. Khedr, Sara I. Taha
{"title":"Interleukin-17A serum levels in young patients with atopic dermatitis and food allergy","authors":"S. Baioumy, D. Sallam, S. Abdalgeleel, S. Fouad, Ahmed S. Khedr, Sara I. Taha","doi":"10.1684/ecn.2021.0470","DOIUrl":"https://doi.org/10.1684/ecn.2021.0470","url":null,"abstract":"Atopic dermatitis (AD) is a common skin disorder accompanied by skin barrier disruption. Patients with AD are commonly affected by food allergy. The present case-control study aimed to assess interleukin-17A (IL-17A) serum levels in children with AD and food allergies and to determine whether increased serum levels of this inflammatory cytokine correlate with disease severity. Healthy control subjects and patients were tested for food allergen reactivity by skin prick test and specific, as well as total, immunoglobulin E (IgE) analysis. IL-17A serum levels were measured by enzyme-linked immunosorbent assay technique. Patients with AD had significantly higher median (interquartile range) serum IL-17A (27 pg/mL [20–35] vs. 7 pg/mL [4.875–15.25]; P < 0.001) and total IgE levels (190 IU/mL [127–279] vs. 26.5 IU/mL [18.75–43.25]; P < 0.001) than controls and 44.6% (37/83) had a positive family history of allergy. Most patients with AD were reactive to two or three food allergens, with milk, eggs and nuts being the most common. No significant correlations were found between IL-17A levels and age and sex of patients, total IgE levels, the number and type of reactive food allergens and disease severity. In the receiver-operating characteristic analysis, the discriminating power of IL-17A and total IgE for AD severity was deficient when used alone but enhanced in combination. Serum IL-17A levels cannot be considered as a reliable AD severity measure and should be combined with other markers in a multimarker technique to enhance its predictive value.","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 1","pages":"55 - 63"},"PeriodicalIF":2.8,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47079045","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":"Upregulated Tie2 expression in plasma: a potential non-invasive biomarker for the diagnosis of breast cancer.","authors":"Qingzhu Song, Fenglan Zhang, Tian Yuan, Yulong Wei","doi":"10.1684/ecn.2021.0468","DOIUrl":"https://doi.org/10.1684/ecn.2021.0468","url":null,"abstract":"<p><p>Breast cancer is by far the most common malignancy found in women and causes a significant public health problem around the world. Early diagnosis of cancer plays an important role in successful treatment and survival of patients. This study aims to investigate the possibility of plasma Tie2 to be used as a biomarker for diagnosis of breast cancer. In total, 20 healthy volunteers and 33 breast cancer patients were considered for this study. The level of Tie2 in plasma was detected using the ELISA technique and immunohistochemistry was performed to measure the expression of Tie2 in normal and breast cancer tissues. Plasma concentrations of Tie2 were significantly higher among breast cancer patients compared to healthy subjects, and both mRNA and protein expression of Tie2 were higher in breast cancer tissue than in normal tissue. Plasma concentrations of Tie2 were positively correlated with the grade of breast cancer. Finally, in vitro knockdown of Tie2 expression in a breast adenocarcinoma cell line inhibited the proliferation of these cells. It is concluded from the results that Tie2 might be a useful plasma biomarker for the early detection of breast cancer and could be developed to be a target for novel drug discovery.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 2","pages":"39-47"},"PeriodicalIF":2.8,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39166839","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}
Francisca Sosa-Jurado, Laura Sánchez-Reza, Miguel Ángel Mendoza-Torres, Daniel Meléndez-Mena, Víctor Hugo García Y García, Belinda Guzmán-Flores, José Antonio Enciso-Moreno, Juan Ernesto López-Ramos, Juan Carlos Balandrán, Verónica Vallejo-Ruiz, Paulina Cortes-Hernández, Julio Reyes-Leyva, Gerardo Santos-López
{"title":"Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals.","authors":"Francisca Sosa-Jurado, Laura Sánchez-Reza, Miguel Ángel Mendoza-Torres, Daniel Meléndez-Mena, Víctor Hugo García Y García, Belinda Guzmán-Flores, José Antonio Enciso-Moreno, Juan Ernesto López-Ramos, Juan Carlos Balandrán, Verónica Vallejo-Ruiz, Paulina Cortes-Hernández, Julio Reyes-Leyva, Gerardo Santos-López","doi":"10.1684/ecn.2021.0466","DOIUrl":"https://doi.org/10.1684/ecn.2021.0466","url":null,"abstract":"<p><p>Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-β, IL-28A, IL-4, IL-5, IL-13, IL-1β, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-β1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 2","pages":"23-30"},"PeriodicalIF":2.8,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39302487","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}
Sinan Saral, Faruk Saydam, Eda Dokumacioglu, Mehtap Atak, Levent Tümkaya, Hüseyin Avni Uydu
{"title":"Effect of white tea consumption on serum leptin, TNF-α and UCP1 gene expression in ovariectomized rats.","authors":"Sinan Saral, Faruk Saydam, Eda Dokumacioglu, Mehtap Atak, Levent Tümkaya, Hüseyin Avni Uydu","doi":"10.1684/ecn.2021.0467","DOIUrl":"https://doi.org/10.1684/ecn.2021.0467","url":null,"abstract":"<p><strong>Background: </strong>Obesity and dyslipidemia due to estrogen deficiency are among the important health problems in menopausal women. Increasing evidence reports the anti-obesity and anti-hyperlipidemic properties of tea polyphenols. However, the effect of white tea (WT) with high polyphenol content on overweight and lipid profile is uncertain. Here, we aimed to examine the effects of long-term WT consumption on serum leptin, tumor necrosis factor- alpha (TNF-α) and uncoupling protein 1 (UCP1) mRNA gene expression in ovariectomized (OVX) rats.</p><p><strong>Methods: </strong>Adult rats were divided into four groups (n = 8): (i) sham, (ii) OVX, (iii) WT and (iv) OVX + WT. WT was given at a dose of 0.5% w/v for 12 weeks. In the study, body weight, serum leptin, TNF, estradiol (E2) levels, lipid profile and UCP1 mRNA gene expression in brown adipose tissue (BAT) were evaluated.</p><p><strong>Results: </strong>There was a significant increase in body weight of OVX rats, which was decreased following WT consumption. While leptin and E2 levels decreased in the OVX group, TNF levels increased. There was no difference between the NF-kB levels of the groups. In addition, BAT UCP1 mRNA expression was significantly decreased in OVX groups, while WT treatment stimulated UCP1 activity.</p><p><strong>Conclusion: </strong>We explain the stimulatory effect of WT on weight loss mainly by the induction of UCP1 gene-mediated thermogenesis and suppression of inflammation. Therefore, we suggest that prolonged WT consumption may have beneficial effects in limiting excess weight gain caused by estrogen deficiency.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 2","pages":"31-38"},"PeriodicalIF":2.8,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39302488","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":"NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-κB and MAPK pathways.","authors":"Xin Zhang, He Nan, Jialong Guo, Jinyu Liu","doi":"10.1684/ecn.2021.0465","DOIUrl":"https://doi.org/10.1684/ecn.2021.0465","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal synovial hyperplasia and the release of inflammatory cytokines. NLRP12 is a member of the family nod-like receptor (NLR) families that are activators of inflammation. However, the role of NLRP12 in fibroblast-like synoviocytes (FLSs) is still unclear. In the present study, we have investigated the role of NLRP12 in fibroblast-like synoviocytes (FLSs). The results demonstrated that NLRP12 overexpression inhibited proliferation and promoted cell apoptosis in RA-FLSs. Moreover, NLRP12 overexpression repressed inflammation by downregulation of IL-1β, TNF-α, IL-6, IFN-γ and MCP-1 production and upregulation of IL-10 levels with knockdown of NLRP12 expression showing opposite effects. In addition, NLRP12 overexpression suppressed phosphorylation of JNK, ERK, p38 and NF-κB in RA-FLSs, whereas NLRP12 knockdown promoted phosphorylation of these proteins. In conclusion, these findings demonstrate that NLRP12 inhibits proliferation and inflammation of RA-FLSs via the regulation of the NF-κB and MAPK signaling pathways, suggesting that NLRP12 might be a potential target for RA treatment.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 2","pages":"15-22"},"PeriodicalIF":2.8,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39302486","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}