AUTHOR=Zhang Yuan , Aldridge Jonathan , Vasileiadis Georgios K. , Edebo Helena , Ekwall Anna-Karin H. , Lundell Anna-Carin , Rudin Anna , Maglio Cristina 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.569883

DOI=10.3389/fimmu.2020.569883

ISSN=1664-3224

ABSTRACT=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). Moreover, elevated circulating adiponectin levels are a risk factor for future development of RA in subjects with obesity. We hypothesize that adiponectin might be 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. Peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) were obtained from non-inflamed subjects and stimulated with 5 μg/ml human recombinant adiponectin. Supernatants collected after 48 hours were analyzed for the production of 13 chemokines and 12 cytokines using multiplex assay and ELISA. Adiponectin significantly stimulated the production of CXCL1, CXCL5, CXCL8, CCL2 and interleukin (IL)-6 in both PBMCs and FLS, whereas it induced CCL3, CCL20, CCL4, CCL17, tumor necrosis factor (TNF), IL-8, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) only in PBMCs and CXCL10, CCL5 and CCL11 only in FLS. 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 indicate that adiponectin stimulates pro-inflammatory responses in non-inflamed cells and support the hypothesis that it might be implicated in the early phases of RA pathogenesis.