Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients
Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients
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DOI：
10.1136/annrheumdis-2011-200096
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发表时间：
2012-01-01
影响因子：
27.4
通讯作者：
Heymann, D.
中科院分区：
文献类型：
--
作者：
Chemel, M.;Le Goff, B.;Heymann, D.
目的白细胞介素（IL） 34是一种参与巨噬细胞分化和破骨细胞形成的新细胞因子。本研究评估了IL-34在类风湿关节炎（RA）患者组织中的表达。方法对风湿性关节炎（20例）、骨关节炎（3例）和其他炎性关节炎（4例）患者的滑膜活检进行免疫组化。用ELISA法检测滑膜液中IL-34的含量，用定量PCR法检测类风湿滑膜成纤维细胞在肿瘤坏死因子α (TNF α)和IL-1 β刺激后IL-34信使RNA的表达。采用野生型、jnk1(-/-) -jnk2（-/-）和nemo（-/-）小鼠成纤维细胞和药物抑制来确定核因子κ B （nf - κ B）和JNK参与了这种作用。结果IL-34在24/27例活检组织中表达，其中3例RA患者活检组织IL-34阴性。IL-34的表达与滑膜炎的严重程度有显著的相关性。滑液中IL-34水平与白细胞总数有相关性。TNF α和IL-1 β通过nf - κ B和JNK通路以剂量/时间依赖的方式刺激滑膜成纤维细胞IL-34的表达。结论本工作首次确定了IL-34在关节炎患者滑膜组织中的表达。这种细胞因子，作为TNF α和IL-1 β的下游效应物，可能有助于RA的炎症和骨侵蚀。
Objectives Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA).Methods Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor alpha (TNF alpha) and IL-1 beta. Wild-type, jnk1(-/-) -jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-kappa B) and JNK in that effect.Results IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNF alpha and IL-1 beta stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-kappa B and JNK pathway.Conclusion This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNF alpha and IL-1 beta, may contribute to inflammation and bone erosions in RA.