Joanna Krajewska Wojciechowska, Katarzyna Kościelska-Kasprzak, Wojciech Krajewski, Krzysztof Morawski
{"title":"Serum levels of interleukin-32 and interleukin-6 in granulomatosis with polyangiitis and microscopic polyangiitis: association with clinical and biochemical findings.","authors":"Joanna Krajewska Wojciechowska, Katarzyna Kościelska-Kasprzak, Wojciech Krajewski, Krzysztof Morawski","doi":"10.1684/ecn.2019.0439","DOIUrl":"https://doi.org/10.1684/ecn.2019.0439","url":null,"abstract":"<p><strong>Background: </strong>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder of unknown etiology with dysregulated cytokines levels.</p><p><strong>Objectives: </strong>The main aim of this study was to assess the clinical correlation between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, granulomatosis with polyangiitis (GPA) serum levels of the microscopic polyangiitis (MPA), serum levels of the proinflammatory cytokines, interleukin (IL)-32 and interleukin-6.</p><p><strong>Methods: </strong>Study included 71 patients, 47 with GPA and 24 with MPA. Serum IL-32 and IL-6 concentrations were analyzed in all patients, and compared with levels observed in 10 controls. IL-32 and IL-6 were evaluated using DuoSet and Quantikine HS ELISA, respectively. IL-32 and IL-6 concentrations were correlated with disease-related clinical and laboratory findings.</p><p><strong>Results: </strong>IL-32 and IL-6 levels were significantly higher in GPA and MPA than in controls, especially IL-32 levels in GPA were elevated. IL-32 concentrations correlated positively with anti-proteinase 3 - ANCA (PR3-ANCA) levels in GPA (P < 0.0001), and with anti-myeloperoxidase ANCA (MPO-ANCA) in MPA (P = 0.049). IL-32 levels correlated positively with disease activity in GPA and MPA (P < 0.0001). GPA patients with pulmonary, cutaneous, and musculoskeletal involvement presented the highest IL-6 serum levels. Cutaneous manifestations correlated positively with IL-6 levels in MPA patients (P = 0.05). ANCA-positive patients with GPA expressed significantly high IL-6 levels (P = 0.036). No significant difference in IL-32 values was observed between ANCA-positive and ANCA-negative patients.</p><p><strong>Conclusions: </strong>Patients with GPA and MPA present higher serum IL-32 and IL-6 levels than controls. IL-32 levels correlate positively with disease activity.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"151-159"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37675794","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}
Sifei Yu, Xi Luo, Binyan Yang, Li Xiao, Xingmei Wu, Huabin Li, Changyou Wu
{"title":"Poly-functional T helper cells in human tonsillar mononuclear cells.","authors":"Sifei Yu, Xi Luo, Binyan Yang, Li Xiao, Xingmei Wu, Huabin Li, Changyou Wu","doi":"10.1684/ecn.2015.0368","DOIUrl":"10.1684/ecn.2015.0368","url":null,"abstract":"<p><p>Tonsils are important lymphoid organs in which B cells and T cells complete their maturation and identify cells that are infected by pathogens. However, the functions of T cells in human tonsils remain unclear, especially the characteristics of polyfunctional CD4<sup>+</sup> T helper cells. In this study, we used multi-color flow cytometry to analyze the expression or co-expression of effector cytokines in CD4<sup>+</sup> T cells from tonsillar tissues. We have demonstrated that tonsillar CD4<sup>+</sup> T cell can express various Th effector cytokines after short-term polyclonal stimulation, and that cytokine-producing CD4<sup>+</sup> T cells were CD45RO<sup>+</sup> T cells. In addition, we analyzed the co-expression of two or more kinds of cytokines at the level of a single cell. The results showed that tonsillar CD4<sup>+</sup> T cells exhibited polyfunctionality by co-expressing two to five kinds of cytokines in the same time. These data furnished a basic theory for further understanding the differentiation of polyfunctional Th cells in human tonsils and their functions in resisting invasive microorganisms.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"114-122"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37676279","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}
Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Farhad Rezaei, Saied Bokaie, Farzaneh Tofighi Zavareh, Fatemeh Kiaee, Ali N Kamali, Gholamreza Azizi, Abbas Mirshafiey
{"title":"Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine.","authors":"Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Farhad Rezaei, Saied Bokaie, Farzaneh Tofighi Zavareh, Fatemeh Kiaee, Ali N Kamali, Gholamreza Azizi, Abbas Mirshafiey","doi":"10.1684/ecn.2019.0435","DOIUrl":"https://doi.org/10.1684/ecn.2019.0435","url":null,"abstract":"<p><strong>Introduction: </strong>Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.</p><p><strong>Method: </strong>Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine.</p><p><strong>Results: </strong>Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21<sup>low</sup> expressing B cells were found.</p><p><strong>Conclusion: </strong>Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21<sup>low</sup> expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"123-129"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2019.0435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37676280","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}
Gautier Breville, Agustina M Lascano, Pascale Roux-Lombard, Patrice H Lalive
{"title":"IL-8 as a potential biomarker in Guillain-Barre Syndrome.","authors":"Gautier Breville, Agustina M Lascano, Pascale Roux-Lombard, Patrice H Lalive","doi":"10.1684/ecn.2019.0436","DOIUrl":"https://doi.org/10.1684/ecn.2019.0436","url":null,"abstract":"<p><p>This pilot study was designed to compare the levels of interleukin-8 (IL-8), a pro-inflammatory chemokine, in the cerebrospinal fluid (CSF) of patients with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), non-inflammatory polyneuropathy (PNP), and other non-inflammatory neurological diseases (functional syndrome or migraine). The results show elevated CSF IL-8 levels in GBS compared to the other groups (p < 0.05). IL-8 could be considered a potential biomarker to differentiate GBS from CIDP. This distinction could be relevant in terms of therapeutic decisions and functional prognosis.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"130-134"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2019.0436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37676281","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":"Effect of folate supplementation on immunological and autophagy markers in experimental nonalcoholic fatty liver disease.","authors":"Sara Youssry, Maher A Kamel","doi":"10.1684/ecn.2019.0437","DOIUrl":"10.1684/ecn.2019.0437","url":null,"abstract":"<p><strong>Background and aims: </strong>Chronic hepatic inflammation is an important pathogenic mediator of nonalcoholic fatty liver disease (NAFLD) that contributes to disease severity. It is commonly suggested that autophagy dysfunction may be an underlying cause of nonalcoholic fatty liver disease. However, the exact role of autophagy in lipid metabolism remains controversial. There has been a growing interest in the role of folate supplementation for the treatment and/or prevention of NAFLD. We aimed in this study to investigate the effects of different doses of folate supplementation on several immune markers and autophagy trying to explore the complex role of IL-22 and autophagy in NAFLD.</p><p><strong>Methods: </strong>Fifty Wistar rats were randomly separated into experimental (n = 40) and control groups (n = 10), which were fed for eight weeks with a high-fat diet (HFD) containing 40% fats or a standard diet, respectively. The experimental group was further subdivided into four subgroups where the first subgroup was left untreated while the other three were treated with different doses of folate (50, 100, and 150 μg/kg of body weight, respectively). At the end of the experimental period, animals from each group were sacrificed for blood and tissue analyses.</p><p><strong>Results: </strong>NAFLD rats showed decreased IL-22 serum levels and increased LC3B expression as compared to controls. Folate treatment was significantly associated with improvement in disease parameters, reduced presence of the pro-inflammatory cytokines TNF-α and CXCL8 and LC3B expression, and increased IL-22 levels in a dose-dependent manner.</p><p><strong>Conclusion: </strong>These results highlight the capacity of folate to modulate the production of several pro-inflammatory cytokines and autophagy thereby having a favorable impact disease progression.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"135-143"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2019.0437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37676282","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}
Katarina Mirjačić Martinović, Milica Milićević, Annette K Larsen, Radan Džodić, Vladimir Jurišić, Gordana Konjević, Ana Vuletić
{"title":"Effect of cytokines on NK cell activity and activating receptor expression in high-risk cutaneous melanoma patients.","authors":"Katarina Mirjačić Martinović, Milica Milićević, Annette K Larsen, Radan Džodić, Vladimir Jurišić, Gordana Konjević, Ana Vuletić","doi":"10.1684/ecn.2019.0440","DOIUrl":"10.1684/ecn.2019.0440","url":null,"abstract":"<p><strong>Objective: </strong>Stage II melanoma patients have high risk for regional and distant metastases and may benefit from novel therapeutic strategies. To clarify the role of NK cells in Stage II melanoma, we characterized the cytotoxic activity of NK cells and the expression of various activating and inhibitory receptors in high-risk cutaneous melanoma patients (Stages IIB and IIC) compared to low-risk patients (Stage IA).</p><p><strong>Materials and methods: </strong>Native and cytokine-treated peripheral blood mononuclear cells were used for functional and phenotypical analyses.</p><p><strong>Results: </strong>Compared to Stage IA-B patients, Stage IIB-C patients showed significantly decreased NK cell activity, as well as decreased expression of the activating NKG2D and CD161 receptors, most likely due to increased serum levels of the immunosuppressive cytokine TGF-β1 in these patients. Interestingly, treatment of periperal blood mononuclear cells with IFN-α, IL-2, IL-12 or the combination of IL-12 and IL-18 significantly induced NK cell activity for both groups of melanoma patients. However, only low-risk patients had a significant increase in the expression of the NKG2D receptor after in vitro treatment with IFN-α, as well as an significant increase in the expression of CD161 after treatment with IFN-α or IL-12. Although IL-2 induced the expression of NKG2D in both groups of patients, this increase was significantly lower in high-risk melanoma.</p><p><strong>Conclusion: </strong>NK cell parameters may be useful as biomarkers of disease progression in localized melanoma patients. Our results further suggest that the use of NK cell-activating cytokines in combination with inhibitors of immunosuppressive factors like TGF-β1 could be a therapeutic option for the treatment of high-risk cutaneous melanoma patients.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"160-167"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37675795","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":"Association of elevated interleukin-33 serum levels with tumorstages in patients with prostate cancer.","authors":"Nazanin Chatrabnous, Abdollah Jafarzadeh, Abass Ghaderi, Ali Ariafar, Najmeh Aminizadeh, Farzaneh Ghassabi, Maryam Nemati","doi":"10.1684/ecn.2019.0438","DOIUrl":"https://doi.org/10.1684/ecn.2019.0438","url":null,"abstract":"<p><strong>Background: </strong>Inflammation has a prominent role in cancer development and interleukin (IL)-33 has both inflammatory and anti-inflammatory properties. The aim of this study was to measure IL-33 quantities and genetic alterations in the rs1929992 SNP within IL-33 gene in patients with prostate cancer (PC).</p><p><strong>Methods: </strong>This investigation was conducted on blood specimens from 150 newly diagnosed PC patients and 150 healthy age-matched controls. Serum IL-33 measurements and genotyping were performed by ELISA and PCR-RFLP, respectively.</p><p><strong>Results: </strong>Elevated IL-33 quantities were detected in PC patients compared with controls (P < 0.001). The PC patients with Gleason scores 7-10 displayed greater IL-33 quantities than those who had Gleason scores 1-6 (P < 0.001). Significant differences were found between PC stages regarding the IL-33 serum levels (P < 0.001). The frequencies of the genotype GG and allele G in rs1929992 SNP were higher, whereas the frequencies of the genotype AA and allele A were lower in PC patients, as compared with controls (P < 0.05, 0.01, P < 0.002 and P < 0.01, respectively). The genotype GG and allele G of rs1929992 SNP were associated with a greater risk of cancer development (OR: 4.533; P < 0.001, and OR: 1.516; P < 0.01, respectively). The IL-33 levels were not significantly different between the subjects carrier genotypes AA, AG and GG, or alleles A and G in rs1929992 SNP, neither in patients nor in controls.</p><p><strong>Conclusion: </strong>Higher IL-33 quantities were found in patients with PC, especially in those with greater stages which raises the possiblity that IL-33 may contribute to PC progression. The rs1929992 SNP-related genotype GG and allele G were associated with an increased risk of cancer development.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"144-150"},"PeriodicalIF":2.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37676283","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}
Mei Ying Cui,Xin Li,Yi Meng Lei,Li Ping Xia,Jing Lu,Hui Shen
{"title":"Effects of IL-34 on the secretion of RANKL/OPG by fibroblast-like synoviocytes and peripheral blood mononuclear cells in rheumatoid arthritis.","authors":"Mei Ying Cui,Xin Li,Yi Meng Lei,Li Ping Xia,Jing Lu,Hui Shen","doi":"10.1684/ecn.2019.0428","DOIUrl":"https://doi.org/10.1684/ecn.2019.0428","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3>To detect the effect of interleukin (IL)-34 on the secretion of Receptor activator of nuclear factor kappa-B ligand (RANKL)/Osteoprotegerin (OPG) and Matrix metalloproteinase (MMP)-3 by fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and to investigate whether the effect is mediated by IL-17.<h3 data-test=\"abstract-sub-heading\">Method</h3>RA-FLS and RA-PBMCs were stimulated with recombinant human (rh) IL-34, with or without the IL-17 inhibitor Plumbagin. The supernatant of the culture medium was collected and the levels of RANKL, OPG, and MMP-3 were detected by enzyme-linked immunosorbent assay (ELISA).<h3 data-test=\"abstract-sub-heading\">Results</h3>RhIL-34 promoted RANKL secretion and inhibited OPG secretion in RA-FLS. The effect was weakened by the addition of the IL-17 inhibitor. In contrast, rhIL-34 had no significant effect on MMP-3 secretion by FLS. RhIL-34 elevated the secretion of RANKL by RA-PBMCs but not by healthy-PBMCs. Furthermore, the secretion of RANKL by RA-PBMCs reduced after the addition of the IL-17 inhibitor. OPG secretion by both RA-FLS and FLS from healthy controls was inhibited by rhIL-34, but were elevated after the addition of the IL-17 inhibitor. RhIL-34 had no significant effect on MMP-3 secretion by both RA-PBMCs and healthy-PBMCs.<h3 data-test=\"abstract-sub-heading\">Conclusion</h3>IL-34 enhances RANKL/OPG expression by RA-FLS and RA-PBMCs, and this effect is, indirectly, mediated by IL-17. This cytokine is therefore likely to to play an important role in local joint destruction and systemic osteoporosis in RA, and is therefore a potential therapeutic target for the treatment of this disease.","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"32 1","pages":"67-73"},"PeriodicalIF":2.8,"publicationDate":"2019-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138533197","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":"IL-38 serum levels in patients with Behcet's disease and the relationship with clinical features.","authors":"Maryam Zarrabi, Nasser Gholijani, Saeedeh Shenavandeh, Elham Aflaki, Zahra Amirghofran","doi":"10.1684/ecn.2019.0430","DOIUrl":"https://doi.org/10.1684/ecn.2019.0430","url":null,"abstract":"<p><p>Behcet's disease (BD) is a chronic multisystem autoimmune disorder. Various cytokines take part in the pathogenesis of this disease. Interleukin (IL)-38, a new member of IL-1 cytokine family, has been reported to have anti-inflammatory properties; however, its role in BD has not been investigated yet. In this study, we aimed to examine the probable role of IL-38 in the clinical context of BD. A total of 81 patients with BD and 81 age- and sex-matched healthy subjects as controls were included in this study. The serum levels of IL-38 were measured in patients and controls sera using enzyme-linked immunosorbent assay. The relationship between the serum levels of IL-38 and clinical and laboratory characteristics of the patients were determined. IL-38 serum levels were significantly lower in patients in comparison with healthy controls at P = 0.003. We found significant differences between IL-38 levels in BD patients with positive and negative pathergy tests (P = 0.048) and patients with and without eye involvement (P = 0.046). Despite the absence of significant differences in serum levels between male and female patients, IL-38 levels were higher in female patients with a positive pathergy test (P = 0.048) and those patients with eye involvement (P = 0.046). As healthy controls showed higher IL-38 serum levels than patients, a protective anti-inflammatory role of IL-38 in BD is suggested. Together, these results suggest that the positive relationship between IL-38 serum levels and eye involvement that IL-38 may play a role in this clinical feature of the disease.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 3","pages":"82-87"},"PeriodicalIF":2.8,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2019.0430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37558856","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":"lncRNA NEAT1 regulates fibrosis and inflammatory response induced by nonalcoholic fatty liver by regulating miR-506/GLI3.","authors":"Si-Si Jin, Xian-Fan Lin, Ju-Zeng Zheng, Qiong Wang, Hua-Qin Guan","doi":"10.1684/ecn.2019.0432","DOIUrl":"https://doi.org/10.1684/ecn.2019.0432","url":null,"abstract":"<p><p>As one of the most common liver disorders worldwide, nonalcoholic fatty liver disease (NAFLD) begins with the abnormal accumulation of triglyceride (TG) in the liver and can lead to inflammation and fibrosis. Long noncoding RNA (lncRNA) NEAT1 was reported to promote NAFLD progress. However, its molecular mechanism in NAFLD was not fully clear. In vitro cellular model of NAFLD was established with BRL3A cell treated by free fatty acid (FFA). Cell Counting Kit-8 (CCK-8) assay was carried out to assess cell proliferation. The expression of mRNA and protein of inflammation and fibrosis in BRL3A cell was detected by qRT-PCR and Western blot. Bioinformatics and dual-luciferase reporter assays were used to predict and validate the interaction between NEAT1 and miR-506 as well as GLI3 and miR-506. NEAT1 was upregulated while miR-506 was downregulated in the progression of NAFLD. Meanwhile, NEAT1 and miR-506 were proved to regulate fibrosis, inflammatory response, and lipid metabolism. Knockdown of NEAT1 inhibited GLI3 expression and promoted miR-506 expression, Overexpression of miR-506 inhibited NEAT1 and GLI3 expression. Moreover, dual-luciferase reporter assays proved that miR-506 could bind to NEAT1 and GLI3, whereas NEAT1 could sponge miR-506 to regulate GLI3 expression. lncRNA NEAT1 could regulate fibrosis, inflammatory response, and lipid metabolism via the miR-506/GLI3 axis as a ceRNA, which is a novel mechanistic role in the regulation of NAFLD. These results provide a new potential treatment target for NAFLD.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 3","pages":"98-106"},"PeriodicalIF":2.8,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2019.0432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37558783","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}