The role of interleukin-17 in inducible nitric oxide synthase-mediated nitric oxide production in endothelial cells

Cell Mol Life Sci. 2003 Mar;60(3):518-25. doi: 10.1007/s000180300043.

Abstract

The effect of interleukin (IL)-17 on the activation of inducible nitric oxide (NO) synthase (iNOS) and subsequent production of NO was investigated. IL-17 induced NO production in both mouse and rat endothelial cells in a dose- and time-dependent manner. This was paralleled by the induction of mRNA for iNOS, which was markedly down-regulated by specific antagonists of protein tyrosine kinase, p38 MAP kinase or iNOS transcription factor NF-kappaB. The expression of iNOS transcription factor IRF-1 was also induced by IL-17 and blocked by all three inhibitors, suggesting that the induction of iNOS by IL-17 might be partly exerted through IRF-1 activation. Neutralization with the specific antibody showed that endogenous IL-17 is involved in T cell-mediated NO production in endothelial cells and NO-dependent suppression of T cell growth. These data indicate that IL-17-triggered iNOS activation in endothelial cells might participate in regulation of the T cell-dependent inflammatory response.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Endothelium, Vascular / metabolism
  • Fibroblasts / metabolism
  • Interferon Regulatory Factor-1
  • Interleukin-17 / metabolism*
  • Mice
  • Myocardium / metabolism*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / metabolism*
  • Phosphoproteins / metabolism
  • Rats
  • T-Lymphocytes / metabolism

Substances

  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Interleukin-17
  • Irf1 protein, mouse
  • Irf1 protein, rat
  • Phosphoproteins
  • Nitric Oxide
  • Nitric Oxide Synthase