Pirilä L, Heino J
Department of Medical Biochemistry, MediCity Research Laboratory, University of Turku, Finland.
J Rheumatol. 1996 Oct;23(10):1691-8.
We recently showed that in rheumatoid arthritis (RA) the extracellular matrix around the lining cells is similar to the matrix seen in osteoarthritis, whereas the cellular adhesion apparatus is very different. In hyperplastic synovial membrane there is very little of alpha 6, alpha v, and beta 5 integrin subunits, whereas in noninflammatory synovial membrane these integrins are well expressed. We studied how expression of these cell adhesion molecules is regulated in RA in vitro.
The integrin expression in 6 different synovial fibroblast strains representing the type B cells and in THP-1 cell line was examined by immunoprecipitation, flow cytometry, and Northern hybridization.
Proinflammatory cytokines, especially interleukin 1 beta, increased the expression of alpha 1 integrin in synovial fibroblasts. When the monocyte-like THP-1 cells were induced to differentiate to adherent macrophages they started to express alpha 6 and beta 5 integrin subunits. In adherent THP-1 cells the expression of integrin alpha 6 subunit was strongly enhanced by transforming growth factor-beta and downregulated by the combination of tumor necrosis factor-alpha and interferon-gamma.
Cytokines regulate the cell adhesion molecules of synovial fibroblasts and mononuclear phagocytes in vitro causing alterations in integrin expression similar to the ones seen in rheumatoid synovium in vivo.
我们最近发现，在类风湿关节炎（RA）中，衬里细胞周围的细胞外基质与骨关节炎中的基质相似，而细胞黏附装置则有很大不同。在增生性滑膜中，α6、αv和β5整合素亚基很少，而在非炎性滑膜中这些整合素表达良好。我们研究了这些细胞黏附分子在体外RA中的表达是如何调控的。
通过免疫沉淀、流式细胞术和Northern杂交检测了代表B型细胞的6种不同滑膜成纤维细胞株和THP-1细胞系中的整合素表达。
促炎细胞因子，尤其是白细胞介素1β，增加了滑膜成纤维细胞中α1整合素的表达。当单核细胞样THP-1细胞诱导分化为贴壁巨噬细胞时，它们开始表达α6和β5整合素亚基。在贴壁的THP-1细胞中，转化生长因子-β强烈增强整合素α6亚基的表达，而肿瘤坏死因子-α和干扰素-γ的联合作用则使其下调。
细胞因子在体外调节滑膜成纤维细胞和单核吞噬细胞的细胞黏附分子，导致整合素表达的改变，类似于体内类风湿滑膜中所见的情况。
