Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.
Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.
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Interleukin-29 增强骨关节炎中的滑膜炎症和软骨退化
DOI：
10.1155/2016/9631510
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发表时间：
2016
影响因子：
4.6
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Xu L;Peng Q;Xuan W;Feng X;Kong X;Zhang M;Tan W;Xue M;Wang F
我们最近发现IL-29是类风湿关节炎（RA）发病机制中的重要促炎细胞因子。炎症也有助于骨关节炎（OA）的发病机制。本研究旨在探讨IL-29对OA软骨细胞因子产生和软骨降解的影响及其机制。与健康对照组（HC）相比，OA患者外周血单个核细胞（PBMC）中IL-29及其特异性受体IL-28 Ra的mRNA水平显著升高。血清IL-29蛋白水平OA组高于HC组。免疫组织化学显示，与HC相比，OA滑膜中的IL-29和IL-28 Ra均显著升高;滑膜成纤维细胞（FLS）和巨噬细胞是OA滑膜中主要的IL-29产生细胞。此外，重组IL-29增强了OA FLS中IL-1β、IL-6、IL-8和基质金属蛋白酶-3（MMP-3）的mRNA表达，并且当离体OA软骨外植体与OA FLS共孵育时，增加了软骨降解。Western blot结果显示，IL-29在OA FLS中主要激活MAPK和核因子-κB（NF-κB），而不激活Jak-STAT和AKT信号通路。总之，IL-29通过OA FLS刺激炎症和软骨降解，表明这种细胞因子可能参与OA的发病机制。
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.