Endogenous IL-1α from systemic sclerosis fibroblasts induces IL-6 and PDGF-A
Endogenous IL-1α from systemic sclerosis fibroblasts induces IL-6 and PDGF-A
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DOI：
10.1172/jci4304
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发表时间：
1999-05-01
影响因子：
15.9
通讯作者：
Wright, TM
中科院分区：
文献类型：
--
作者：
Kawaguchi, Y;Hara, M;Wright, TM
据报道，源自系统性硬化症（SSc）患者临床受影响皮肤区域的成纤维细胞能够过量产生多种细胞因子和生长因子（即IL-6、PDGF），这种能力可能与SSc的发病机制有关。我们之前已经表明，在 SSc 成纤维细胞中持续观察到 IL-1 α 的表达，而在正常成纤维细胞中未检测到。尽管有人认为异常的 IL-1 α 产生可能与 SSc 成纤维细胞的纤维形成表型有关，但人们对 IL-1 α 在 SSc 成纤维细胞中的作用知之甚少。 IL-1 α 诱导 IL-6 和 PDGF-A，它们是正常成纤维细胞中胶原蛋白生成和增殖的有效刺激剂。本文探讨了以下观点：IL-6 和 PDGF-A 通过 SSc 成纤维细胞中内源性 IL-1 α 的作用而升高。使用与 IL-1 α mRNA 互补的反义寡脱氧核苷酸来抑制内源性 IL-1 α。抑制内源性 IL-1 α 导致 SSc 成纤维细胞中 IL-6 和 PDGF-A 表达水平降低。此外，使用抗IL-6抗体阻断IL-6反应导致培养的SSc成纤维细胞中I型前胶原显着减少。这些结果表明，SSc成纤维细胞表达的内源性IL-1α可能通过IL-6和PDGF-A的表达在SSc成纤维细胞功能异常中发挥关键作用。
It is reported that fibroblasts derived from clinically affected skin areas of patients with systemic sclerosis (SSc) have the ability to overproduce several cytokines and growth factors (i.e., IL-6, PDGF), an ability that might be involved in the pathogenesis of SSc. We have previously shown that the expression of IL-1 alpha was constitutively observed in SSc fibroblasts, whereas this was not detected in normal fibroblasts. Although it was suggested that the aberrant IL-1 alpha production could be associated with the fibrogenic phenotype of SSc fibroblasts, little is known about the roles of IL-1 alpha in SSc fibroblasts. IL-1 alpha induced IL-6 and PDGF-A, which are potent stimulators of collagen production and proliferation in normal fibroblasts. This article examines the proposal that IL-6 and PDGF-A are elevated through the action of endogenous IL-1 alpha in SSc fibroblasts. An antisense oligodeoxynucleotide complementary to IL-1 alpha mRNA was used to suppress endogenous IL-1 alpha. Inhibition of endogenous IL-1 alpha led to decreased levels of IL-6 and PDGF-A expression in SSc fibroblasts. Moreover, the blocking of the IL-6 response using anti-IL-6 antibody resulted in a significant reduction of procollagen type I in cultured SSc fibroblasts. These results suggest that endogenous IL-1 alpha expressed by SSc fibroblasts may play a key role in the abnormal function of SSc fibroblasts through the expression of IL-6 and PDGF-A.