Gamma interferon prevents the inhibitory effects of oxidative stress on host responses to Escherichia coli infection.
Oxidative stress occurs in animals challenged with bacterial endotoxin and can affect the expression of important host inflammatory genes. However, much less is known about the effects of oxidative stress on responses to gram-negative bacteria. The current study compared the effects of redox imbalance on hepatic responses of mice to Escherichia coli bacteria versus purified endotoxic lipopolysaccharide (LPS). Oxidative stress induced by glutathione depletion virtually eliminated hepatic tumor necrosis factor alpha responses to both E. coli and LPS. Inducible NO synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) expression was also markedly inhibited by glutathione depletion in LPS-challenged mice, but was unaffected in E. coli-infected animals. Three findings suggested that gamma interferon (IFN-gamma) production explained the differences between LPS and bacterial challenge. Glutathione depletion completely inhibited the IFN-gamma response to LPS, but only partially inhibited IFN-gamma production in infected mice. Exogenous IFN-gamma restored iNOS and ICAM-1 responses to LPS in stressed mice. Conversely, IFN-gamma-deficient, glutathione-depleted mice showed a marked decrease in iNOS and ICAM-1 expression when challenged with E. coli. These findings indicate that both the nature of the microbial challenge and the production of IFN-gamma can be important in determining the effects of redox imbalance during gram-negative bacterial infections.
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160-7420, USA. mparmely@kumc.edu
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Wang
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D000818:Animals; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress
D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005978:Glutathione