Cigarette smoke decreases inducible nitric oxide synthase in lung epithelial cells

Jeffrey C. Hoyt, Richard A. Robbins, Michael Habib, David R. Springall, Lee D.K. Buttery, Julia M. Polak, Peter J. Barnes

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Cigarette smoking has been associated with decreased exhaled nitric oxide (NO). To investigate the mechanism of this decrease, the effects of a cigarette smoke extract were evaluated a murine lung epithelial cell line (LA-4), a human lung epithelial cell line (A549), and primary cultures of human lung epithelial cells induced to produce NO by cytokines. NO production was evaluated by measuring nitrite, a stable end product of NO, in cell culture supernatant fluids. Cigarette smoke extract caused a reduction in the cytokine-induced nitrite concentrations in the culture supernatant fluids from all 3 cell types (P <.01, all comparisons). To further investigate these observations, immunohistochemistry demonstrated a decrease in cytokine-induced inducible NO synthase (iNOS) protein expression and iNOS mRNA after cigarette smoke extract exposure in LA-4 cells. However, iNOS mRNA half-life was not altered by the smoke extract, suggesting that the smoke extract decreased NO by decreasing iNOS mRNA transcription. These findings demonstrate that cigarette smoke extract decreases iNOS expression and NO production from lung epithelial cells.

Original languageEnglish (US)
Pages (from-to)17-28
Number of pages12
JournalExperimental Lung Research
Issue number1
StatePublished - Jan 2003
Externally publishedYes


  • Cigarette smoke
  • Lung epithelial cells
  • Nitricoxide
  • iNOS

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry


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