Cytokine modulation of murine microglial cell superoxide production.
Activated microglia may contribute to two opposite effects during inflammation within the central nervous system: host defense against microorganisms and neuronal injury. Each of these processes may be mediated by the generation of reactive oxygen intermediates by activated microglia. We investigated the effects of two proinflammatory cytokines, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and of the anti-inflammatory cytokine, transforming growth factor (TGF)-beta, on murine microglial cell superoxide (O2-) production upon stimulation with phorbol myristate acetate (PMA). Priming of microglia with IFN-gamma or TNF-alpha resulted in a dose-dependent enhancement of O2- release in response to PMA. The priming effects of these two cytokines were additive, suggesting that they acted by independent mechanisms. We also found that IFN-gamma and TNF-alpha stimulated the release of bioactive TGF-beta and that treatment of microglial cell cultures with TGF-beta antagonized the priming effects of IFN-gamma and TNF-alpha on O2- production. The results of this study have implications for understanding the mechanisms by which cytokines and microglia may contribute to host defense as well as to injury of the brain.
Hu
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Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Sheng
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WS
Peterson
P K
PK
Chao
C C
CC
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004357:Drug Synergism; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate