Antioxidant activities and redox regulation of interferon-gamma-induced tryptophan metabolism in human monocytes and macrophages.
This article summarises studies supporting the proposal that induction of L-tryptophan (Trp) degradation along the kynurenine pathway in human monocytes and macrophages by interferon-gamma (IFN gamma) represents a novel extracellular antioxidant defence that acts to prevent inadvertent oxidative damage to host tissue during inflammation. The studies show that formation and release of the aminophenolic antioxidant 3-hydroxyanthranilic acid (3-HAA) is responsible for the ability of IFN gamma-primed human macrophages to inhibit the oxidation of low density lipoprotein (LDL); an event implicated as an important event in atherogenesis. 3-HAA efficiently inhibits LDL oxidation by acting as an aqueous oxidant scavenger and a synergist for LDL-associated vitamin E. Indoleamine 2,3-dioxygenase activity (IDO) is the initial and rate limiting enzyme of Trp degradation along the kynurenine pathway. Nitric oxide inhibits IDO activity in IFN gamma-primed human macrophages and this may represent a physiological regulatory mechanism of the dioxygenase during inflammation.
Thomas
S R
SR
Biochemistry Group, Heart Research Institute, Sydney, Australia.
Stocker
R
R
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction; D014364:Tryptophan / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D015095:3-Hydroxyanthranilic Acid; D007371:Interferon-gamma; D014364:Tryptophan