Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes.
The effect of interleukin-17 (IL-17) on production of nitric oxide (NO) in rodent astrocytes was investigated. While IL-17 by itself did not induce NO production, it caused a dose-dependent enhancement of IFN-gamma-triggered NO synthesis in both mouse and rat primary astrocytes. In contrast, IL-17 was unable to stimulate NO synthesis in either murine or rat macrophages. IFN-gamma-triggered expression of mRNA for iNOS, but not for its transcription factor interferon regulatory factor-1 (IRF-1), was markedly elevated in IL-17-treated astrocytes. The induction of iNOS mRNA by IL-17 in IFN-gamma-pretreated astrocytes was abolished by antagonists of nuclear factor-kappaB (NF-kappaB) activation--a proteasome inhibitor MG132 and an antioxidant agent PDTC, as well as with specific p38 MAP kinase inhibitor SB203580. While IL-17 stimulated both IL-1beta and IL-6 production in astrocytes, only IL-1 was partly responsible for IL-17-induced NO release. Finally, IL-17 synergized with exogenous IL-1beta and TNF-alpha for astrocyte NO production. Having in mind a well-known neurotoxic action of NO, these results suggest a possible role for IL-17 in the inflammatory diseases of the CNS.
Trajkovic
V
V
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000, Belgrade, Yugoslavia.
Stosic-Grujicic
S
S
Samardzic
T
T
Markovic
M
M
Miljkovic
D
D
Ramic
Z
Z
Mostarica Stojkovic
M
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D001254:Astrocytoma; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D007375:Interleukin-1; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat