The role of interleukin-17 in inducible nitric oxide synthase-mediated nitric oxide production in endothelial cells.
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.
Miljkovic
Dj
Dj
Institute for Biological Research Sinisa Stankovic, 29 Novembra 142, 11060 Belgrade, Yugoslavia. georgije.zw@yahoo.com
Cvetkovic
I
I
Vuckovic
O
O
Stosic-Grujicic
S
S
Mostarica Stojkovic
M
M
Trajkovic
V
V
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D020381:Interleukin-17; C494258:Irf1 protein, mouse; C494259:Irf1 protein, rat; D010750:Phosphoproteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase