Nicotine enhancement of lipopolysaccharide/interferon-γ-induced cytotoxicity with elevating nitric oxide production

Yen Chou Chen, Shing Chuan Shen, Hui Yi Lin, Shu Huei Tsai, Tony J F Lee

研究成果: 雜誌貢獻文章

14 引文 斯高帕斯(Scopus)

摘要

Nicotine has been shown to induce relaxation via nitric oxide (NO) production with activation of endothelium nitric oxide synthase (eNOS), however the effect of nicotine on lipopolysaccharide/interferon-γ (LPS/IFN-γ)-induced NO production and inducible NOS (iNOS) gene expression is still undefined. Here, nicotine alone did not affect the NO and PGE 2 production in RAW264.7 and primary peritoneal macrophages. Interestingly, nicotine showed the dose-dependent stimulatory effect on LPS (20 ng/ml)/IFN-γ (10 ng/ml)-induced NO but not PGE2 production in both cells. Although nicotine stimulates NO production in the presence of LPS/IFN-γ, LPS at the dose of 20 ng/ml, nicotine showed no obvious inductive effect on the expression of iNOS protein by Western blotting in both cells. However, nicotine significantly stimulates LPS (2.5, 5 ng/ml)/IFN-γ (10 ng/ml)-induced iNOS expression and NO production in RAW264.7 cells. Cytotoxicity assay showed that nicotine enhanced LPS (20 ng/ml) and IFN-γ (10 ng/ml)-induced cytotoxicity, which was inhibited by an NOS inhibitor N-nitro-L-arginine (NLA) in RAW264.7 cells. Direct and indirect NOS activity assays indicated that nicotine did not affect NOS activity. And, iNOS protein stability was not changed by nicotine after LPS/IFN-γ treatment. These data indicates that nicotine may potentiate LPS/IFN-γ-induced cytotoxic effects by enhancing NO production; enhancing iNOS gene expression induced by LPS/IFN-γ is involved. A cross-talk between inflammation and smoking was proposed in the present study.

原文英語
頁(從 - 到)191-200
頁數10
期刊Toxicology Letters
153
發行號2
DOIs
出版狀態已發佈 - 十一月 2 2004

    指紋

ASJC Scopus subject areas

  • Toxicology

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