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Lipid mediator interplay: resolvin D1 attenuates inflammation evoked by glutathione-conjugated lipid peroxidation products
Authors:János G Filep
Institution:1.Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, QC, Canada;2.Department of Pathology and Cell Biology, University of Montreal, Montreal, QC, Canada
Abstract:Non-enzymatic oxidation of cellular lipids, one of the characteristic features of inflammation, leads to formation of highly reactive and toxic α,β-unsaturated aldehydes, such as 4-hydroxy-trans-2-nonenal (HNE). Conjugation of HNE with reduced glutathione (GS-HNE) is widely believed to represent a form of detoxification. The study by Spite et al. in the current issue of the British Journal of Pharmacology shows that glutathiolation of HNE confers potent pro-inflammatory properties on this α,β-unsaturated aldehyde. They find that GS-HNE directly activates human neutrophil granulocytes in vitro and evokes peritonitis in mice. Pre-treatment with resolvin D1, which is derived from ω-3 fatty acids, markedly attenuated the peritoneal leukocyte accumulation and production of prostaglandins and leukotrienes induced by GS-HNE. Their findings have profound implications for the analysis of inflammation in describing the generation of a novel class of pro-inflammatory mediators, through glutathione-dependent metabolism of lipid-peroxidation products, and emphasize the therapeutic potential of resolvin D1 in inflammatory diseases.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
Keywords:4-hydroxy-trans-2-nonenal  oxidative stress  glutathione  resolvin D1  neutrophil granulocytes  eicosanoids  adhesion molecules  peritonitis  inflammation  resolution of inflammation
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