RA滑膜成纤维细胞产生的IL34有促破骨细胞生成作用

RA滑膜成纤维细胞产生的IL34有促破骨细胞生成作用

徐 宁

        摘要  研究背景：白介素-34是一种最新定义的的细胞因子，与巨噬细胞集落刺激因子(M-CSF)具有类似的生理功能。本研究检测了类风湿关节炎患者白介素-34的表达，并且探讨了它在类风湿关节炎患者的病理机制中的调节作用。

        研究方法：白介素-34的水平在类风湿关节炎患者滑膜、关节滑液以及滑膜成纤维细胞中被检测，检测方法应用了免疫组织化学法，实时PCR方法，与ELISA方法以及免疫印迹法。类风湿关节炎活动度应用DAS28评分在基线水平及治疗一年后进行评估。应用肿瘤坏死因子a刺激24小时的类风湿关节炎患者滑膜成纤维细胞产生的培养基上清作为条件培养基，进行功能试验检测。

        研究结果：白介素-34在类风湿关节炎患者滑膜、关节滑液以及滑膜成纤维细胞中表达与骨性关节炎相比，应用肿瘤坏死因子a刺激后的类风湿关节炎患者滑膜成纤维细胞产生的白介素-34是上调的。更重要的是肿瘤坏死因子a刺激产生的白介素-34比巨噬细胞集落刺激因子(M-CSF) 刺激产生的白介素-34更多，并且通过核转录因子kB通路介导产生并且激活JNK激酶。白介素-34在类风湿关节炎患者的基线水平是升高的，在DMARDs药物作用后出现下降，并与DAS28评分的下降趋势一致。应用肿瘤坏死因子a刺激后的类风湿关节炎患者滑膜成纤维细胞产生的培养基上清可促进人外周血单核细胞的化学迁移以及破骨细胞形成，并且这些效应可被抗白介素-34抗体减弱。

        研究结论：研究数据揭示新发现，即白介素-34可在在类风湿关节炎患者滑膜、关节滑液以及滑膜成纤维细胞中表达，而且白介素-34是另一个受肿瘤坏死因子a调节的破骨细胞生成因素，提示了白介素-34在炎症性类风湿关节炎中的调节作用。

        附原文: ABSTRACT: INTRODUCTION: Interleukin-34 (IL-34) is a recently defined cytokine, showing a functional overlap with macrophage colony stimulating factor (M-CSF). This study was undertaken to address the expression of IL-34 in rheumatoid arthritis (RA) patients and to investigate its regulation and pathogenic role in RA. METHODS: IL-34 levels were determined in the RA synovium, synovial fluid (SF) and fibroblast-like synovial cells (FLS) by immunohistochemistry, real-time PCR, enzyme-linked immunosorbent assay and immunoblotting. RA activity was assessed using Disease Activity Score 28 (DAS28) activity in the plasma collected at baseline and 1-yr after treatment. Conditioned media (CM) was prepared from RA FLS culture with tumor necrosis factor alpha (TNFa) for 24 h and used for functional assay.  RESULTS: IL-34 was expressed in the synovium, SF, and FLS from RA patients. The production of IL-34 in FLS was up-regulated by TNFa in RA samples compared with osteoarthritis (OA) patients. Importantly, the preferential induction of IL-34 rather than M-CSF by TNFa in RA-FLS was mediated by the transcription factor nuclear factor kappa B (NF-kappaB) and activation of c-Jun N-terminal kinase (JNK). IL-34 elevation in plasma from RA patients was decreased after disease-modifying anti-rheumatic drugs (DMARDs) administration in accordance with a decrease in DAS28. CM from RA-FLS cultured with TNFa promoted chemotactic migration of human peripheral blood mononuclear cells (PBMCs) and subsequent osteoclast (OC) formation, effects that were attenuated by an anti-IL-34 antibody. CONCLUSIONS: These data provide novel information about the production of IL-34 in RA FLS and indicate that IL-34 is an additional osteoclastogenic factor regulated by TNFa in RA, suggesting a discrete role of IL-34 in inflammatory RA diseases.

        引自：Interleukin-34 produced by human fibroblast-like synovial cells in rheumatoid arthritis supports osteoclastogenesis.  Arthritis Res Ther. 2012 Jan 20;14(1):R14. [Epub ahead of print]