Zhang Yuan, Aldridge Jonathan, Vasileiadis Georgios K, Edebo Helena, Ekwall Anna-Karin H, Lundell Anna-Carin, Rudin Anna, Maglio Cristina
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Front Immunol. 2021 Feb 1;11:569883. doi: 10.3389/fimmu.2020.569883. eCollection 2020.
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.
脂联素是一种脂肪因子，在新陈代谢中起调节作用，具有抗炎和促炎双重效应。类风湿关节炎（RA）患者血清和滑液中的脂联素水平升高。脂联素能够刺激已确诊RA患者外周血单核细胞（PBMC）和成纤维样滑膜细胞（FLS）产生不同的促炎因子。由于循环脂联素水平升高是肥胖受试者未来发生RA的危险因素，我们推测脂联素通过启动与疾病发病机制相关的促炎过程，在RA早期发展中发挥作用。因此，我们旨在确定脂联素是否能够在参与RA发病机制但取自无任何已知炎症性疾病受试者的细胞中诱导促炎反应。从非炎症受试者获取PBMC和FLS，并用5μg/ml人重组脂联素进行刺激。48小时后收集上清液，使用多重检测和酶联免疫吸附测定（ELISA）分析13种趋化因子和12种细胞因子的产生情况。脂联素显著刺激PBMC和FLS中CXCL1、CXCL5和白细胞介素（IL）-6的产生，而它仅在PBMC中诱导CCL20、CCL4、CCL3、CCL17、肿瘤坏死因子（TNF）、粒细胞巨噬细胞集落刺激因子和IL-10，仅在FLS中诱导CXCL8、CXCL10、CCL5、CCL11和CCL2。与单独使用脂联素相比，用TNF预刺激非炎症受试者的FLS，大多数促炎因子的释放没有显著增强。我们的研究结果表明，来自非炎症受试者的PBMC和FLS对脂联素刺激有反应，分泌多种促炎趋化因子和细胞因子。这些结果表明脂联素能够在来自非炎症受试者的细胞中引发促炎反应，并支持脂联素参与RA发病机制早期阶段的假说。
