Inhibition of inducible nitric oxide synthase expression by interleukin-4 and interleukin-13 in human lung epithelial cells

Immunology. 1996 Nov;89(3):363-7. doi: 10.1046/j.1365-2567.1996.d01-745.x.


Nitric oxide produced by the inducible enzyme, nitric oxide synthase (iNOS), is implicated in immunological and inflammatory processes. We determined the effects of T-helper (Th)2-derived cytokines on the induction of iNOS from an epithelial A549 cell line and human airway epithelial cells stimulated by a mixture of interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Interleukin-4 (IL-4) and interleukin-13 (IL-13) but not interleukin-10 (IL-10) inhibited both iNOS mRNA expression and nitrite release in A549 cells. On human airway epithelial cells, IL-4 and IL-13 reduced iNOS mRNA expression. Dexamethasone also inhibited both iNOS expression and nitrite release. Th2 cytokines, IL-4 and IL-13, inhibit iNOS upregulation by Th1 cytokines, indicating an important reciprocal role of Th1 and Th2 T-cell subsets on lung epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cell Culture Techniques
  • Cytokines / immunology
  • Dose-Response Relationship, Immunologic
  • Epithelium / enzymology
  • Epithelium / immunology
  • Gene Expression Regulation, Enzymologic / immunology
  • Humans
  • Interleukin-13 / immunology*
  • Interleukin-4 / immunology*
  • Lung / enzymology
  • Lung / immunology*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • RNA, Messenger / genetics
  • Recombinant Proteins / immunology
  • Tumor Cells, Cultured


  • Cytokines
  • Interleukin-13
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-4
  • Nitric Oxide
  • Nitric Oxide Synthase