Propofol inhibits lipoteichoic acid-induced iNOS gene expression in macrophages possibly through downregulation of toll-like receptor 2-mediated activation of Raf-MEK1/2-ERK1/2-IKK-NFκB

Wen Ta Chiu, Yi Ling Lin, Chih Wei Chou, Ruei Ming Chen

研究成果: 雜誌貢獻文章同行評審

34 引文 斯高帕斯(Scopus)

摘要

Our previous study showed that propofol suppressed Gram-negative bacterial LPS-induced NO biosynthesis. Lipoteichoic acid (LTA), an outer membrane component of Gram-positive bacteria, can induce septic shock. This study was further aimed to evaluate the effects of propofol on LTA-induced iNOS gene expression in macrophages and its possible molecular mechanisms. Exposure of macrophages to LTA increased production of nitrite and intracellular reactive oxygen species, but propofol reduced such enhancements in concentration- and time-dependent manners. Treatment of macrophages with LTA-induced iNOS mRNA and protein productions. Meanwhile, propofol at a clinically relevant concentration of 50 μM significantly inhibited LTA-caused augmentations of iNOS mRNA and protein syntheses. In parallel, exposure to LTA increased translocation of nuclear factor-kappa B (NFκB) from the cytoplasm to nuclei. Propofol at 50 μM decreased such translocation. Analyses by an electrophoretic mobility shift and reporter gene further showed that propofol could alleviate LTA-induced transactivation of NFκB. Sequentially, propofol decreased phosphorylation of IKK, ERK1/2, MEK1/2, and Raf in LTA-stimulated macrophages. Application of toll-like receptor 2 (TLR2) small interference (si)RNA decreased the translation of this receptor and Raf phosphorylation in LTA-stimulated macrophages. Co-treatment with propofol and TLR2 siRNA synergistically ameliorated LTA-induced iNOS mRNA expression and nitrite production. Thus, this study shows that propofol can downregulate NO biosynthesis via inhibiting iNOS gene expression. The suppressive mechanism occurs possibly through reduction of TLR2-mediated sequential activation of Raf-MEK1/2-ERK1/2-IKK-NFκB.

原文英語
頁(從 - 到)430-439
頁數10
期刊Chemico-Biological Interactions
181
發行號3
DOIs
出版狀態已發佈 - 十月 30 2009
對外發佈

ASJC Scopus subject areas

  • 毒理學

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