Oxidative stress and gene expression in sepsis.
Dysregulation of the immuno-inflammatory response, as seen in sepsis, may culminate in host cell and organ damage. Lipopolysaccharide from Gram-negative bacterial cell walls induces gene activation and subsequent inflammatory mediator expression. Gene activation is regulated by a number of transcription factors at the nuclear level, of which nuclear factor kappaB appears to have a central role. The redox (reduction-oxidation) cellular balance is important for normal cellular function, including transcription factor regulation. In sepsis, a state of severe oxidative stress is encountered, with host endogenous antioxidant defences overcome. This has implications for cellular function and the regulation of gene expression. This review gives an overview of the mechanisms by which transcription factor activation and inflammatory mediator overexpression occur in sepsis, together with the events surrounding the state of oxidative stress encountered and the effects on the host's antioxidant defences. The effect of oxidative stress on transcription factor regulation is considered, together with the role of antioxidant repletion in transcription factor activation and in sepsis in general. Other interventions that may modulate transcription factor activation are also highlighted.
Macdonald
J
J
Academic Unit of Anaesthesia and Intensive Care, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
Galley
H F
HF
Webster
N R
NR
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000627:therapeutic use; D001665:Binding Sites; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D015870:Gene Expression / Q000235:genetics*; D005786:Gene Expression Regulation; D005978:Glutathione / Q000627:therapeutic use; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics* / Q000276:immunology; D010100:Oxygen / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017382:Reactive Oxygen Species / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014810:Vitamin E; D005978:Glutathione; D001205:Ascorbic Acid; D010100:Oxygen; D004121:Dimethyl Sulfoxide