IL-33 regulates TNF-α dependent effects in synovial fibroblasts.
IL-33 regulates TNF-α dependent effects in synovial fibroblasts.
复制标题
IL-33调节滑膜成纤维细胞中TNF-α的依赖性效应。
DOI：
10.3892/ijmm.2012.883
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发表时间：
2012-04
影响因子：
5.4
通讯作者：
Kinne RW
中科院分区：
文献类型：
--
作者：
Kunisch E;Chakilam S;Gandesiri M;Kinne RW
最近描述的IL-33作为促炎细胞因子，诱导靶细胞中多种应答的表达。虽然已经描述了IL-33的核定位，但其确切的功能相关性目前尚不清楚。本研究采用RNA过表达和沉默技术分析IL-33对TNF-α诱导的类风湿关节炎滑膜成纤维细胞（RA-SFs）合成促炎介质IL-6、IL-8和单核细胞趋化蛋白-1（MCP-1）以及促破坏分子基质金属蛋白酶-1（MMP-1）、MMP-3和TIMP-1的影响。TNF-α可显著诱导RA SF中IL-33 mRNA表达和蛋白合成。TNF-α诱导的IL-33蛋白表达通过p38信号转导介导。IL-33的免疫组化结果显示TNF-α刺激RA-SFs后IL-33发生核转位。IL-33过表达增强了TNF-α诱导的RA-SFs的促炎和促破坏功能。IL-33沉默显著下调TNF-α诱导的促炎功能，而TNF-α诱导的促破坏功能受IL-33沉默的影响较小。本研究将IL-33确定为RA-SF中TNF-α诱导功能的关键调节剂/增强剂，指出该细胞因子在类风湿性关节炎（RA）和其他炎症和退行性疾病的促炎和促破坏过程中的持续作用。
The recently described IL-33 acts as a pro-inflammatory cytokine, inducing the expression of multiple responses in the target cells. Although a nuclear localization of IL-33 has been described, its exact functional relevance is presently unknown. The present study was conducted to analyze the effects of IL-33 on the TNF-α induced synthesis of the pro-inflammatory mediators IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the pro-destructive molecules matrix metalloproteinase-1 (MMP-1), MMP-3, and TIMP-1 of rheumatoid arthritis synovial fibroblast (RA-SFs) using RNA overexpression and silencing. TNF-α significantly induced IL-33 mRNA expression and protein synthesis in RA-SFs. TNF-α-induced IL-33 protein expression was mediated via p38 signaling. Immunohistochemistry for IL-33 clearly showed that nuclear translocation of IL-33 was induced in TNF-α stimulated RA-SFs. IL-33 overexpression enhanced TNF-α-induced pro-inflammatory and pro-destructive functions in RA-SFs. IL-33 silencing significantly downregulated TNF-α-induced pro-inflammatory functions, whereas TNF-α-induced pro-destructive functions were less influenced by IL-33 silencing. This study identifies IL-33 as a critical regulator/enhancer of TNF-α-induced functions in RA-SFs, pointing to a central role of this cytokine in the perpetuation of pro-inflammatory and pro-destructive processes in rheumatoid arthritis (RA) and other inflammatory and degenerative diseases.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
影响因子：
4.4
作者：
Leung, BP;Xu, D;Liew, FY
通讯作者：
Liew, FY
DOI：
10.1186/ar391
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Hirth A;Skapenko A;Kinne RW;Emmrich F;Schulze-Koops H;Sack U
通讯作者：
Sack U
影响因子：
5
作者：
Iikura, Motoyasu;Suto, Hajime;Nakae, Susumu
通讯作者：
Nakae, Susumu
影响因子：
6
作者：
Baekkevold, ES;Roussigné, M;Girard, JP
通讯作者：
Girard, JP