Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients
Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients
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DOI：
10.1016/j.joca.2014.12.007
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发表时间：
2015-11-01
影响因子：
7
通讯作者：
Houard, X.
中科院分区：
文献类型：
--
作者：
Deligne, C.;Casulli, S.;Houard, X.
目的：骨关节炎（OA）相关滑膜炎是几种临床症状的直接原因，反映了OA的结构进展。本研究旨在分析促炎介质的表达，包括白细胞介素(IL)-17和IL-22，它们在调节炎症过程中起关键作用，在骨关节炎滑膜的炎症和非炎症区域。方法：对32例OA患者术中膝关节滑膜进行采集。炎症的宏观评价使炎症区和非炎症区分开。将样品孵育以获得组织条件培养基。RT-PCR定量分析促炎介质mRNA表达，ELISA和明胶酶谱法定量分析促炎介质蛋白水平。进行免疫组化和组织学检查。结果：与非炎症组织相比，炎症滑膜的特征是白细胞浸润增加，血管与组织面积之比更高。巨噬细胞、T淋巴细胞、B淋巴细胞和部分中性粒细胞仅存在于炎症组织中，且仅存在于内膜下层。炎症组织条件培养基中促炎细胞因子和MMP-9的水平明显高于非炎症组织。炎症区域与IL-17和IL-22的高表达相关，两者均与IL-6、IL-23和TGF β的联合释放相关(1)。结论：炎性因子IL-17和IL-22在骨性关节炎滑膜中表达水平升高，提示IL-22参与骨性关节炎的病理生理。本研究将有助于确定新的OA治疗策略，特别是靶向IL-22减少炎症。(C) 2014年由Elsevier Ltd代表国际骨关节炎研究学会出版。
Objective: Synovitis associated with osteoarthritis (OA) is directly responsible for several clinical symptoms and reflects OA's structural progression. This study sought to analyze the expression of proinflammatory mediations, including Interleukin (IL)-17 and IL-22, which play key roles in regulating inflammatory processes, in inflamed and non-inflamed areas of osteoarthritic synovium.Methods: Synovium from knees of 32 OA patients were collected at surgery. Macroscopic evaluation of inflammation enabled inflamed and non-inflamed areas to be separated. Samples were incubated to obtain tissue-conditioned media. Quantitative mRNA expression of proinflammatory mediators was analyzed by RT-PCR and protein levels by ELISA and gelatin zymography. Immunohistochemistry and histology were performed.Results: Inflamed synovium were characterized by increased leukocyte infiltration and a higher vessel-to-tissue area ratio than non-inflamed tissues. Macrophages, T and B lymphocytes, and some neutrophils were found only in the inflamed tissue, and only in the subintimal layer. Levels of proinflammatory cytokines and MMP-9 were significantly higher in tissue-conditioned media from inflamed than non-inflamed tissues. Inflamed areas were associated with higher expression of IL-17 and IL-22, both correlated with the combined release of IL-6, IL-23, and TGF beta(1).Conclusion: Our results showed that inflammatory cytokines, including IL-17 and IL-22, are expressed at higher levels by inflamed OA synovium and suggest IL-22 involvement in OA pathophysiology. This study will help identify new therapeutic strategies for OA, especially the targeting of IL-22 to decrease inflammation. (C) 2014 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.