Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators

Academic Article

Abstract

  • Nitroalkene derivatives of linoleic acid (LNO2) and oleic acid (OA-NO2) are present; however, their biological functions remain to be fully defined. Herein, we report that LNO2 and OA-NO2 inhibit lipopolysaccharide-induced secretion of proinflammatory cytokines in macrophages independent of nitric oxide formation, peroxisome proliferator-activated receptor-γ activation, or induction of heme oxygenase-1 expression. The electrophilic nature of fatty acid nitroalkene derivatives resulted in alkylation of recombinant NF-κB p65 protein in vitro and a similar reaction with p65 in intact macrophages. The nitroalkylation of p65 by fatty acid nitroalkene derivatives inhibited DNA binding activity and repressed NF-κB-dependent target gene expression. Moreover, nitroalkenes inhibited endothelial tumor necrosis factor-α-induced vascular cell adhesion molecule 1 expression and monocyte rolling and adhesion. These observations indicate that nitroalkenes such as LNO2 and OA-NO 2, derived from reactions of unsaturated fatty acids and oxides of nitrogen, are a class of endogenous anti-inflammatory mediators. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Cui T; Schopfer FJ; Zhang J; Chen K; Ichikawa T; Baker PRS; Batthyany C; Chacko BK; Feng X; Patel RP
  • Start Page

  • 35686
  • End Page

  • 35698
  • Volume

  • 281
  • Issue

  • 47