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

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14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalToxicology Letters
Volume153
Issue number2
DOIs
Publication statusPublished - Nov 2 2004

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Keywords

  • BCIP
  • COX-2
  • cyclooxygenase 2
  • dithiothreitol
  • DTT
  • IFN-γ
  • inducible nitric oxide synthase
  • iNOS
  • interferon-γ
  • lipopolysaccharide
  • LPS
  • N-nitro-L-arginine
  • NBT
  • nitric oxide
  • nitroblue tetrazolium
  • NLA
  • NO
  • PGE
  • prostaglandin E2

ASJC Scopus subject areas

  • Toxicology

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