Expression and function of chemerin in synovial tissues of patients with rheumatoid arthritis

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type:TOHO University Scholarly Publication

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Background: Chemerin is an adipokine that stimulates chemotaxis of cells involved in the innate immune system. We evaluated the role of chemerin in inflammatory arthritides such as rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative PCR were used to detect messenger ribonucleic acid (mRNA) for chemerin and chemerin receptor23 (ChemR23) in 20 patients with RA and 10 patients with OA. In addition, the effect of chemerin on matrix metalloproteinase (MMP) production by cultured synovial cells was assessed. Results: Chemerin mRNA expression was higher in RA synovium than in OA synovium (3.01±3.84 vs 1.00±1.84, p=0.024). ChemR23 mRNA expression was also higher in RA synovium than in OA synovium (2.43±2.95 vs 1.00±1.02, p=0.035). Chemerin induced expression of MMP-1, MMP-3, and MMP-13 mRNA in RA synovium via ChemR23, but did not induce expression of MMP-2, tissue-inhibitor of metalloproteinases (TIMP)-1, or TIMP-2. Chemerin stimulated the extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway via ChemR23. Chemerin-induced MMP-1/3 and MMP-13 expression was suppressed by an ERK1/2 inhibitor and an Akt inhibitor. Conclusions: Chemerin is produced locally in patients with inflammatory arthritides such as RA, and ChemR23 is an important target of chemerin in synovial tissues of patients with RA. Activated chemerin has a proinflammatory effect in inflamed joints. These findings could lead to development of new therapeutic approaches for inflammatory arthritis. 目的:関節リウマチ(rheumatoid arthritis:RA)滑膜病変におけるアディポカイン chemerin の発現と作用について検討した.方法:RA および変形性関節症(osteoarthritis:OA)滑膜病変における chemerin と chemerin 受容体chemerin receptor 23(ChemR23)の発現を real-timePCR および免疫組織化学にて測定した.また RA 培養滑膜細胞に interleukin-1(IL-1)を添加し chemerin 産生誘導と chemerin による滑膜細胞からの matrixmetalloproteinase(MMP)の誘導を測定した.結果:RA 滑膜組織は OA 滑膜組織と比較し chemerin,ChemR23 を強く発現していた.IL-1 は滑膜細胞から chemerin を濃度依存的に誘導した.Chemerin は滑膜細胞からの MMP-1,3,13 messenger ribonucleicacid(mRNA)を誘導し,この効果は extracellular signal-regulated kinase 1/2(ERK-1/2),Akt 阻害にて抑制された.結論:Chemerin は RA 滑膜より産生誘導され,MMP 産生を介して RA 関節炎の病態形成に関与していると考えられた.

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