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Inhibition of interferon‐gamma‐induced nitric oxide production in BV‐2 microglial cells by polyphenolic compounds
Author(s) -
Zheng Q.,
Binek J.,
Sun G. Y.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.17_7.x
Subject(s) - genistein , microglia , resveratrol , nitric oxide , chemistry , quercetin , cytokine , pharmacology , biochemistry , polyphenol , tyrosine kinase , nitric oxide synthase , microbiology and biotechnology , signal transduction , biology , antioxidant , inflammation , immunology , endocrinology , organic chemistry
Microglial cells are known to play an important role in mediating the host defense functions in the brain. These cells respond readily to pro‐inflammatory cytokines, which stimulate signalling pathways and induction of many genes, including the inducible nitric oxide synthase (iNOS). In the immortalized BV‐2 microglial cells, our studies have demonstrated that interferon gamma (IFNγ) alone could stimulate the induction of iNOS through activation of the nuclear factor‐kappa B (NF‐κB) pathway. Increased NO production in the brain has been implicated in enhanced oxidative stress associated with many neurodegenerative diseases. Many polyphenolic compounds in vegetables and fruits, including resveratrol, catechin, quercetin, genistein are regarded as phytoestrogens and are known to possess potent antioxidant properties. However, whether these compounds also offer anti‐inflammatory effects and inhibit cytokine‐induced NO production in microglial cells have not been examined in detail. The major goal for this project is to use BV‐2 microglial cells as cell model to investigate the effects of these polyphenolic compounds on IFNγ induction of NO. Results show that all the polyphenolic compounds tested could inhibit NO production albeit to different extents, with quercetin having the lowest IC50 and catechin the highest IC50. Surprising, daidzin, a non‐tyrosine kinase analog of genistein, also inhibited IFNγ‐induced NO production, suggesting that the inhibitory effects may not be due entirely to their action on the tyrosine kinase pathway. These results lead to the conclusion that polyphenolic compounds tested not only possess antioxidative but also anti‐inflammatory properties. Acknowledgements: Supported by 5 P01 ES10535 from NIH.