Different regulation of factor H and FHL-1/reconectin by inflammatory mediators and expression of the two proteins in rheumatoid arthritis (RA)
Different regulation of factor H and FHL-1/reconectin by inflammatory mediators and expression of the two proteins in rheumatoid arthritis (RA)
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DOI：
10.1046/j.1365-2249.2000.01285.x
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发表时间：
2000-08-01
影响因子：
4.6
通讯作者：
Zipfel, PF
中科院分区：
文献类型：
--
作者：
Friese, MA;Hellwage, J;Zipfel, PF
因子H和FHL-1/Recectin蛋白是两种人血浆蛋白，其充当补体旁路途径的重要调节剂。每种蛋白质都由独特的转录本编码，但两种mRNA都是通过替代加工从因子H基因衍生而来的。为了解决这两种蛋白质之间的潜在功能差异，我们分析了它们在肝细胞和非肝细胞中的表达，并研究了它们通过炎症介质的调节。我们证明，H因子和FHL-1/reconectin的转录本，这是由相同的基因启动子调控，并在相同的转录起始位点启动不同的表达。这些分子的表达由炎症介质干扰素-γ（IFN-γ）和抗炎糖皮质激素地塞米松诱导和调节。因子H和FHL-1/Recectin均由滑膜成纤维细胞表达和分泌，并存在于来自患有类风湿性或反应性关节炎的患者的滑液中。滑膜成纤维细胞中的局部合成以及IFN-γ和地塞米松对其的诱导，而不是肿瘤坏死因子-α，表明两种补体调节剂中的每一种在RA中具有保护作用。
Factor H and the FHL-1/reconectin protein are two human plasma proteins that act as important regulators of the alternative complement pathway. Each protein is encoded by a unique transcript, but both mRNAs are derived from the factor H gene by means of alternative processing. In order to address potential functional differences between the two proteins we analysed their expression in hepatic and non-hepatic cells and studied their regulation by inflammatory mediators. We demonstrate that factor H and FHL-1/reconectin transcripts which are regulated by the same gene promoter and are initiated at the same transcription start site are differently expressed. Expression of the molecules is induced and regulated by the inflammatory mediators interferon-gamma (IFN-gamma) and the anti-inflammatory glucocorticoid dexamethasone. Both factor H and FHL-1/reconectin are expressed and secreted by synovial fibroblasts and are present in synovial fluid derived from patients suffering from rheumatoid or reactive arthritis. The local synthesis in synovial fibroblasts and their induction by IFN-gamma and dexamethasone, but not by tumour necrosis factor-alpha, suggests for each of the two complement regulators a protective role in RA.