Recombinant Adiponectin Induces the Production of Pro-Inflammatory Chemokines and Cytokines in Circulating Mononuclear Cells and Fibroblast-Like Synoviocytes From Non-Inflamed Subjects

被引:14
作者
Zhang, Yuan [1 ,2 ]
Aldridge, Jonathan [1 ]
Vasileiadis, Georgios K. [1 ,2 ]
Edebo, Helena [3 ]
Ekwall, Anna-Karin H. [1 ]
Lundell, Anna-Carin [1 ]
Rudin, Anna [1 ]
Maglio, Cristina [1 ,2 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden
[2] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
[3] Kungalv Hosp, Clin Orthoped, Kungalv, Sweden
基金
瑞典研究理事会;
关键词
adiponectin; inflammation; chemokines; cytokines; peripheral blood mononuclear cells; fibroblast-like synoviocytes;
D O I
10.3389/fimmu.2020.569883
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Adiponectin is an adipokine with a modulatory role in metabolism and exerting both anti- and pro-inflammatory effects. Levels of adiponectin are increased in serum and synovial fluid from patients with rheumatoid arthritis (RA). Adiponectin is able to stimulate the production of different pro-inflammatory factors from peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) from subjects with established RA. As increased circulating adiponectin levels are a risk factor for future development of RA in subjects with obesity, we hypothesize that adiponectin is implicated in the development of RA at an early stage by initiating the pro-inflammatory processes associated with the disease pathogenesis. Therefore, we aimed to determine if adiponectin is able to induce pro-inflammatory responses in cells involved in the pathogenesis of RA, but collected from subjects without any known inflammatory disease. PBMCs and FLS were obtained from non-inflamed subjects and stimulated with 5 mu g/ml human recombinant adiponectin. Supernatants collected after 48 h were analyzed for the production of 13 chemokines and 12 cytokines using multiplex assay and ELISA. Adiponectin significantly stimulated the production of CXCL1, CXCL5, and interleukin (IL)-6 in both PBMCs and FLS, whereas it induced CCL20, CCL4, CCL3, CCL17, tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor and IL-10 only in PBMCs, and CXCL8, CXCL10, CCL5, CCL11, and CCL2 only in FLS. Pre-stimulation with TNF of FLS from non-inflamed subjects did not significantly enhance the release of most pro-inflammatory factors compared to adiponectin alone. Our findings indicate that PBMCs and FLS from non-inflamed subjects react to adiponectin stimulation with the secretion of several pro-inflammatory chemokines and cytokines. These results suggest that adiponectin is able to initiate pro-inflammatory responses in cells from non-inflamed subjects and support the hypothesis that adiponectin is implicated in the early phases of RA pathogenesis.
引用
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页数:9
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