Transforming growth factor β1 and laminin-111 cooperate in the induction of interleukin-16 expression in synovial fibroblasts from patients with rheumatoid arthritis
Transforming growth factor β1 and laminin-111 cooperate in the induction of interleukin-16 expression in synovial fibroblasts from patients with rheumatoid arthritis
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DOI：
10.1136/ard.2008.091116
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发表时间：
2010-01-01
影响因子：
27.4
通讯作者：
Aicher, W. K.
中科院分区：
文献类型：
--
作者：
Warstat, K.;Hoberg, M.;Aicher, W. K.
目的：在类风湿性关节炎（RA）患者的滑膜组织中，层粘连蛋白和整合素的强表达与炎性细胞因子的表达增加共定位。滑膜成纤维细胞（SF）通过增加细胞因子和趋化因子（其中之一是白细胞介素-16（IL-16））的表达参与RA的发病机制。本研究旨在探讨RA和OA-SF中IL 16的调控途径。采用定量RT-PCR、免疫印迹和ELISA检测IL 16的表达，细胞迁移实验检测IL 16的生物活性。通过细胞结合和附着试验研究细胞-基质相互作用。相关的细胞内信号转导通路进行了研究，通过免疫印迹和药理学阻断reagents.Results：刺激SF与转化生长因子β（1）（TGF-β（1））和生长层粘连蛋白-111（LM-111）显着增加IL 16的表达。与LM-111结合后，RA-SF中IL 16 mRNA的表达显著高于OA-SF（p
Objectives: In synovial tissues of patients with rheumatoid arthritis (RA), strong expression of laminins and integrins co-localises with increased expression of inflammatory cytokines. Synovial fibroblasts (SF) contribute to the pathogenesis of RA through increased expression of cytokines and chemoattractant factors, one of which is interleukin-16 (IL16). A study was undertaken to investigate the regulatory pathways of IL16 in SF from patients with RA (RA-SF) and osteoarthritis (OA-SF).Methods: SF were seeded in laminin-coated flasks and activated by the addition of cytokines. The expression of IL16 was investigated by quantitative RT-PCR, immunoblotting and ELISA; its biological activity was determined by a cell migration assay. Cell-matrix interactions were investigated by cell binding and attachment assays. Relevant intracellular signalling pathways were studied by immunoblotting and with pharmacological blocking reagents.Results: Stimulation of SF with transforming growth factor beta(1) (TGF-beta(1)) and growth on laminin-111 (LM-111) significantly increased the expression of IL16. Binding to LM-111 induced significantly more IL16 mRNA in RA-SF than in OA-SF (p