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. I FN-gamma -triggered expression of mRNA for iNOS, but not for its transcript ion 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-kapp aB (N kappa -KB) activation-a proteasome inhibitor MG132 and an antioxidant agent PDTC, as well as with specific p38 MAP kinase inhibitor SB203580. Wh ile IL-17 stimulated both IL-1 beta and IL-6 production in astrocytes, only IL-1 was partly responsible for IL-17-induced NO release. Finally, IL-17 s ynergized with exogenous IL-1 beta and TNF-alpha for astrocyte NO productio n. Having in mind a well-known neurotoxic action of NO, these results sugge st a possible role for IL-17 in the inflammatory diseases of the CNS. (C) 2 001 Elsevier Science B.V. All rights reserved.