Interacting monocytes and synoviocytes induce adhesion molecules by a cytokine-regulated process.
Interacting monocytes and synoviocytes induce adhesion molecules by a cytokine-regulated process.
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相互作用的单核细胞和滑膜细胞通过细胞因子调节过程诱导粘附分子。
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
M. Macaro
中科院分区：
文献类型：
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作者：
M. Blue;P. Conrad;D. L. Webb;T. Sarr;M. Macaro
单核细胞/巨噬细胞和滑膜成纤维细胞样细胞在滑膜中密切接触，并被认为在类风湿性关节炎的发展中起关键作用。我们研究了体外单核细胞-滑膜细胞相互作用对细胞因子释放和粘附分子表达的影响。使用一个敏感的蛋白质印迹分析，我们发现，VCAM-1和ICAM-1的表达上调后，滑膜细胞共培养。这种相互作用还导致TNF和IL-6在培养基中积累，但不导致IFN-γ在培养基中积累。单核细胞-滑膜细胞样品的培养上清液有效地诱导滑膜细胞中的粘附分子。抗TNF部分抑制VCAM-1和ICAM-1表达的增加，表明TNF部分介导VCAM-1和ICAM-1表达。有趣的是，细胞因子和粘附分子的诱导不需要单核细胞和滑膜细胞之间的细胞接触，这表明细胞通过可溶性因子进行通讯。T细胞因子增强单核细胞-滑膜细胞相互作用诱导的粘附分子的诱导。IFN-γ和IL-4由不同的辅助性T细胞亚群产生，对单核细胞-滑膜细胞相互作用有不同的影响。IFN-γ对滑膜成纤维细胞表达VCAM-1的影响最小，但与单核细胞协同作用，显著上调ICAM-1的表达。IL-4对ICAM-1表达无影响，但可增强单核细胞诱导的VCAM-1表达。我们的研究结果表明，单核细胞-滑膜细胞相互作用后粘附分子的上调是由可溶性因子介导的，并可由特定的T细胞细胞因子调节。
Monocytes/macrophages and synovial fibroblast-like cells are in intimate contact in the synovium and are believed to play a critical role in the development of rheumatoid arthritis. We investigated the effects of monocyte-synoviocyte interactions in vitro on cytokine release and the expression of adhesion molecules. Using a sensitive Western blot assay, we found that VCAM-1 and ICAM-1 expression were up-regulated in synoviocytes following coculture. The interaction also resulted in the accumulation of TNF and IL-6, but not IFN-gamma in the culture medium. Culture supernatant from monocyte-synoviocyte samples effectively induced adhesion molecules in synoviocytes. Anti-TNF partially inhibited the increase in VCAM-1 and ICAM-1 expression, indicating that TNF in part mediates VCAM-1 and ICAM-1 expression. Interestingly, the induction of cytokines and adhesion molecules did not require cell contact between monocytes and synoviocytes, suggesting cell communication via soluble factors. T cell cytokines enhanced the induction of adhesion molecules induced by the monocyte-synoviocyte interaction. IFN-gamma and IL-4, which are produced by distinct T helper subsets, had differential effects on monocyte-synoviocyte interactions. IFN-gamma had a minimal effect on VCAM-1 expression by synovial fibroblasts, but synergized with monocytes to dramatically up-regulate ICAM-1 expression. IL-4 had no effect on ICAM-1 expression but enhanced monocyte-induced expression of VCAM-1. Our results demonstrate that the up-regulation of adhesion molecules following monocyte-synoviocyte interactions is mediated by soluble factors and can be regulated by specific T cell cytokines.