Interleukin-6 inhibits endothelial nitric oxide synthase activation and increases endothelial nitric oxide synthase binding to stabilized caveolin-1 in human vascular endothelial cells

Ming Jui Hung, Wen Jin Cherng, Ming Yow Hung, Hsiao Ting Wu, Jong Hwei S. Pang

研究成果: 雜誌貢獻文章同行評審

55 引文 斯高帕斯(Scopus)

摘要

Objective: We hypothesized a possible mechanism for atherosclerosis in which interleukin-6 (IL-6) might affect the endothelial nitric oxide synthase (eNOS)-caveolin-1 interaction and result in decreased nitric oxide bioavailability in the setting of low-grade inflammation. Methods: Because eNOS and caveolin-1 are crucial for vascular tone control, we studied the effects of IL-6 on the expression and activation of eNOS and caveolin-1 in human vascular endothelial cells. Results: IL-6 inhibited the phosphorylation of eNOS at Ser1177 and the bradykinin-stimulated nitric oxide production; however, eNOS protein expression was not changed. In addition, IL-6 inhibited bradykinin-stimulated Akt phosphorylation at Ser473 and Thr 308 without affecting the Akt protein expression. IL-6 did not alter the mRNA level of caveolin-1; however, the caveolin-1 protein level was significantly increased dose-dependently. The binding of eNOS and caveolin-1 in endothelial cells, as demonstrated by coimmunoprecipitation assay, was increased by IL-6 treatment. IL-6 treatment was found to stabilize caveolin-1 protein and its half-life was estimated to prolong from 7.5 h to longer than 12 h. Furthermore, treatment with PD98059 and short interference RNA of extracellular signal-regulated kinase gene reversed the effects of IL-6 on eNOS and caveolin-1. Conclusion: In addition to decreasing Akt phosphorylation, the results of this study demonstrate, for the first time, the molecular mechanism underlying the effect of IL-6 to decrease the nitric oxide bioavailability by increasing the half-life and, therefore, the protein levels of caveolin-1. The increased caveolin-1 proteins bind more eNOS and consequently decrease eNOS activation by reducing the Ser1177 phosphorylation.

原文英語
頁(從 - 到)940-951
頁數12
期刊Journal of Hypertension
28
發行號5
DOIs
出版狀態已發佈 - 五月 2010
對外發佈

ASJC Scopus subject areas

  • 內科學
  • 生理學
  • 心臟病學與心血管醫學

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