Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells
Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells
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DOI：
10.1159/000079706
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Johnson, RJ
中科院分区：
文献类型：
--
作者：
Watanabe, S;Mu, W;Johnson, RJ
背景/目的：IL-6是急性期反应的诱导剂，与血管疾病和动脉粥样硬化的发生有关。其中一种机制可能与IL-6对血管平滑肌细胞（VSMC）的直接作用有关，因为IL-6可以诱导血管平滑肌细胞增殖和单核细胞化学引诱蛋白-1 （MCP-1）的释放。我们假设这种刺激通过JAK (janus-activated kinase)/STAT （signal and transducers and activators of transcription）信号通路发生。方法：在JAK 2抑制剂存在或不存在的情况下，用IL-6刺激大鼠VSMC，测定STAT 3 （Western）、MCP-1 （ELISA）和DNA合成（h -3胸腺嘧啶结合）的激活情况。结果：IL-6以剂量和时间依赖性的方式快速诱导STAT 3磷酸化，并在30min达到峰值表达。IL-6也刺激MCP-1蛋白的产生和DNA的合成。AG490是一种特异性的JAK 2抑制剂，50mum部分抑制STAT 3的激活和MCP-1的产生，几乎完全抑制DNA合成。结论：JAK/STAT通路部分介导il -6诱导的VSMC MCP-1生成和DNA合成。这些研究暗示了JAK/STAT通路在血管疾病和动脉粥样硬化发展中的作用。版权所有(C) 2004 S. Karger AG，巴塞尔。
Background/Aims: IL-6, an inducer of the acute-phase response, is linked with the development of vascular disease and atherosclerosis. One mechanism likely involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 can induce VSMC proliferation and the release of monocyte chemoattractant protein-1 (MCP-1). We hypothesized that this stimulation occurs via the JAK (janus-activated kinase)/STAT (signal and transducers and activators of transcription) signaling pathway. Methods: Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1 (by ELISA) and DNA synthesis (by H-3-thymidine incorporation) was determined. Results: IL-6 rapidly induced phosphorylation of STAT 3 in a dose- and time-dependent manner with a peak expression at 30 min. IL-6 also stimulated MCP-1 protein production and DNA synthesis dose dependently. 50 muM of AG490, a specific JAK 2 inhibitor, partially inhibited STAT 3 activation and MCP-1 production, with near complete inhibition of DNA synthesis. Conclusion: The JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in the development of vascular disease and atherosclerosis. Copyright (C) 2004 S. Karger AG, Basel.