Suppression of nitric oxide formation by tyrosine kinase inhibitors in murine N9 microglia

British Journal of Pharmacology
B P LockhartJ M Lepagnol

Abstract

1. Microglial cells represent the first line of defence in the brain against infection and damage. However, under conditions of chronic inflammation and neurodegeneration, excessive activation of microglia can contribute to the neurodegenerative process by releasing a cornucopia of potentially cytotoxic substances including the cytotoxic free radical nitric oxide (NO). Although the cell signalling events implicated in NO formation in peripheral macrophages are well defined, events occurring in the phenotypically homologous cerebral microglial cell are not yet fully characterized. 2. In the present study, a cloned murine microglial cell line (N9), stimulated with combined lipopolysaccharide/interferon-gamma (LPS/IFN) incubation, was shown to produce a significant increase in NO formation, as measured by medium nitrite levels, during 8-72 h exposure. 3. LPS/IFN-stimulated NO production was partially inhibited with the nitric oxide synthase (NOS) competitive antagonists; N(omega)-nitro-L-arginine methyl ester and N(omega)-nitro-L-arginine. The ability of the selective inducible (iNOS) inhibitor, aminoguanidine, but not the selective 'neuronal-type' constitutive (cNOS) inhibitor 7-nitroindazole, to inhibit NO production suggested a...Continue Reading

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Citations

Mar 8, 2005·Journal of Neuroimmunology·Filomena O DimayugaAnnadora J Bruce-Keller
Oct 2, 2003·European Journal of Pharmacology·Amanpreet SinghShrinivas K Kulkarni
Jun 5, 2003·Pharmacology & Therapeutics·Michael J Strong
Jul 29, 2000·Neurochemistry International·Y NakamuraK Kataoka
Mar 7, 2003·Journal of Neuroimmunology·Filomena O DimayugaAnnadora J Bruce-Keller
Mar 15, 2008·Journal of Neuroscience Research·Jadwiga Turchan-CholewoAnnadora J Bruce-Keller
Feb 23, 2000·Experimental Neurology·R GriffithJ G Wood
Nov 25, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Srinivas J KammanadimintiKris Chadee
Sep 27, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Beverley A MooreAnthony J Bauer

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