Yamasaki S, Nakashima T, Kawakami A, Miyashita T, Tanaka F, Ida H, Migita K, Origuchi T, Eguchi K
First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Rheumatology (Oxford). 2004 Apr;43(4):448-52. doi: 10.1093/rheumatology/keh092. Epub 2004 Jan 20.
Our recent work showed that fibroblast-like synovial cells (FLS) could differentiate into adipocyte-like cells in vitro in response to stimulation with peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand. The aim of the present study was to determine the role of cytokines in the regulation of FLS differentiation to adipocyte-like cells.
FLS isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from normal synovial tissues were incubated with the synthetic PPAR gamma ligand troglitazone to induce adipocyte-like differentiation of the cells.
Production of interleukin (IL)-6, IL-8 and matrix metalloproteinase-3 was reduced in adipocyte-like cells compared with FLS. DNA binding activity of nuclear factor kappa B (NF-kappa B) was clearly inhibited in adipocyte-like cells. Cultivation of FLS with interferon gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) or IL-1 beta inhibited the expression of PPAR gamma as well as CCAAT/enhancer binding protein (C/EBP) nuclear activity, and thus suppressed adipocyte-like cell differentiation in vitro.
Our results indicate the importance of PPAR gamma and C/EBP in adipocyte-like cell differentiation of FLS and that the process is influenced by inflammatory cytokines, and suggest that the proinflammatory character of FLS in patients with RA is diminished during adipocyte-like cell differentiation.
我们最近的研究表明，成纤维样滑膜细胞（FLS）在过氧化物酶体增殖物激活受体γ（PPARγ）配体刺激下可在体外分化为脂肪样细胞。本研究的目的是确定细胞因子在调节FLS向脂肪样细胞分化中的作用。
将从类风湿关节炎（RA）和骨关节炎（OA）患者以及正常滑膜组织中分离出的FLS与合成的PPARγ配体曲格列酮一起孵育，以诱导细胞向脂肪样分化。
与FLS相比，脂肪样细胞中白细胞介素（IL）-6、IL-8和基质金属蛋白酶-3的产生减少。核因子κB（NF-κB）的DNA结合活性在脂肪样细胞中明显受到抑制。用干扰素γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）或IL-1β培养FLS可抑制PPARγ的表达以及CCAAT/增强子结合蛋白（C/EBP）的核活性，从而在体外抑制脂肪样细胞的分化。
我们的结果表明PPARγ和C/EBP在FLS向脂肪样细胞分化中具有重要作用，且该过程受炎性细胞因子影响，并提示RA患者FLS的促炎特性在脂肪样细胞分化过程中减弱。
