Pulmonary alveolar epithelial inducible NO synthase gene expression: Regulation by inflammatory mediators

H. H. Gutierrez, B. R. Pitt, M. Schwarz, S. C. Watkins, C. Lowenstein, I. Caniggia, P. Chumley, B. A. Freeman

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Nitric oxide (·NO) is a short-lived mediator that can be induced by different cytokines and lipopolysaccharide (LPS) in a variety of cell types and produces many physiological and metabolic changes in target cells. In the current study, we show that a combination of cytokines, LPS, and zymosan- activated serum (ZAS; called for convenience cytomix Z) induces production of high concentrations of the NO oxidation products nitrite (NO2/-) and nitrate (NO3/-) by cultured rat fetal lung epithelial type II cells in a time-dependent fashion. Interferon-γ and tumor necrosis factor-α alone did not significantly affect ·NO synthesis, whereas ZAS, LPS, and interleukin- 1β caused only a modest increase in formation of ·NO oxidation products. Production of NO2/- and NO3/- was inhibited by N(G)-monomethyl-L-arginine and cycloheximide. After exposure of these cells to a combination of the above cytokines, Escherichia coli LPS, and ZAS (cytomix Z), enhanced inducible nitric oxide synthase (iNOS) expression was indicated by an elevation in steady-state mRNA specific for iNOS (via Northern blot analysis) and increased immunofluorescence for iNOS after cell permeabilization, incubation with anti-iNOS antibody, and treatment with Cy3.18-conjugated rabbit-specific antibody. The extent of inflammatory mediator-induced ·NO production by alveolar epithelium, which exceeds that of other lung cell types, reveals new insight into mechanisms of pulmonary host defense and pathways of free radical-mediated lung injury.

Original languageEnglish (US)
Pages (from-to)L501-L508
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3 12-3
StatePublished - 1995
Externally publishedYes


  • alveolar epithelium
  • alveolar type II cell
  • free radical
  • lung
  • nitric oxide
  • nitric oxide synthase
  • peroxynitrite
  • superoxide

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Pulmonary and Respiratory Medicine
  • Cell Biology


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