Modulation of human microglial cell superoxide production by cytokines.
Reactive oxygen intermediates (e.g., superoxide [O2-]) generated by microglia may play a role in host defense and injury within the central nervous system. We investigated the effect of cytokines on human microglial cell O2- production on stimulation with phorbol myristate acetate. Priming of microglial cell cultures with interferon-gamma or tumor necrosis factor-alpha resulted in a dose- and time-dependent enhancement of O2- production. The priming effects of these cytokines were mediated through a protein kinase C signal transduction pathway. In contrast, astrocytes did not generate detectable O2- on phorbol myristate acetate stimulation. Treatment of microglia with transforming growth factor-beta, interleukin-4, or interleukin-10 suppressed in a dose-dependent manner the priming effects of tumor necrosis factor-alpha and interferon-gamma. The results of this study have implications for understanding the mechanisms by which cytokines and microglia contribute to processes of host defense and neurodegeneration via generation of reactive oxygen intermediates.
Chao
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Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Hu
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Peterson
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001253:Astrocytes / Q000201:enzymology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D017628:Microglia / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; D007546:Isoquinolines; D010879:Piperazines; D013481:Superoxides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate