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). 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 μg/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.
Highlights
Adiponectin is a cytokine mainly secreted by the adipose tissue, a so-called adipokine [1, 2]
We first screened the profile of chemokines produced by peripheral blood mononuclear cells (PBMCs) from non-inflamed subjects stimulated with 5.0 μg/ml adiponectin for 48 h
The increase in adiponectin levels under inflammatory conditions, such as serum and synovial fluid from subjects with rheumatoid arthritis (RA), has raised the hypothesis that this adipokine exerts pro-inflammatory functions together with the already known anti-inflammatory effects described in literature [6, 7, 11, 13]
Summary
Adiponectin is a cytokine mainly secreted by the adipose tissue, a so-called adipokine [1, 2]. Since identified in the 1990s [1], adiponectin have been considered mostly as an anti-inflammatory adipokine, being able to induce the production of interleukin (IL)-10 and reduce tumor necrosis factor (TNF) in macrophages [6, 7]. Adiponectin has pro-inflammatory effects as it is able to promote pro-inflammatory responses in CD4+ T cells and macrophages, such as IFN-g and TNF secretion, respectively [9]. Adiponectin induces the production of IL-6, TNF, CXCL1, and CXCL8 in total T- and B-lymphocytes from healthy subjects [10]
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