Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis
Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis
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Interleukin-29 调节类风湿性关节炎滑膜炎症中促炎细胞因子的产生
DOI：
10.1186/ar4067
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发表时间：
2012-01-01
影响因子：
4.9
通讯作者：
Zhang, Miaojia
中科院分区：
文献类型：
--
作者：
Wang, Fang;Xu, Lingxiao;Zhang, Miaojia
白细胞介素(IL)-29的免疫调节功能最近才被认识到。然而，关于IL-29在类风湿关节炎（RA）发病机制中的作用知之甚少。本研究旨在检测IL-29在RA患者血液、滑膜液（SF）和滑膜中的表达谱，并探讨IL-29对RA滑膜成纤维细胞细胞因子产生的影响。方法采用实时逆转录聚合酶链反应（real-time PCR）检测外周血单核细胞（PBMC）和滑膜中IL-29及其特异性受体IL-28Rα的转录水平。采用酶联免疫分析法（ELISA）测定RA患者血清和滑液（SF）中IL-29的含量，并探讨RA患者血清IL-29水平与疾病活动度的相关性。采用免疫组化和双免疫荧光法检测RA滑膜中IL-29的表达。最后采用real-time PCR检测IL-29刺激后滑膜成纤维细胞中IL-6、IL-8、IL-10、IL-17和基质金属蛋白酶-3 （MMP-3）的表达。结果RA患者PBMC中il -29和IL-28Rα mRNA的表达明显高于健康对照组（HC）。RA组血清循环IL-29水平高于HC组。与骨关节炎（OA） SF相比，RA SF中IL-29水平升高。然而，血清IL-29水平与RA疾病活动无显著相关性。IL-29主要表达于RA滑膜内膜区。此外，IL-29主要在滑膜巨噬细胞和成纤维细胞中表达。暴露于IL-29的RA滑膜成纤维细胞特异性上调IL-6、-8和MMP-3，但下调IL-10。结论本研究首次发现IL-29在RA患者中表达异常，可能通过诱导滑膜成纤维细胞产生促炎因子、趋化因子或基质金属蛋白酶参与RA的发病机制。
IntroductionThe immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts.MethodsThe transcript levels of IL-29 and its specific receptor IL-28Rα in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR.ResultsIL-29 and IL-28Rα mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10.ConclusionsThe findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts.