Nitrated Fatty Acids: Endogenous Anti-inflammatory Signaling Mediators

• Published in: The Journal of biological chemistry 2006-11, Vol.281 (47), p.35686-35698
• Main Authors: Cui, Taixing, Schopfer, Francisco J., Zhang, Jifeng, Chen, Kai, Ichikawa, Tomonaga, Baker Paul, R.S., Batthyany, Carlos, Chacko, Balu K., Feng, Xu, Patel, Rakesh P., Agarwal, Anupam, Freeman, Bruce A., Chen, Yuqing E.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Bone Marrow Cells - metabolism; Fatty Acids - chemistry; Heme Oxygenase (Decyclizing) - genetics; Macrophages - metabolism; Mice; Mice, Knockout; NF-kappa B - chemistry; Nitrogen - chemistry; PPAR gamma - metabolism; Protein Processing, Post-Translational; Recombinant Proteins - chemistry; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M603357200

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-NO2, derived from reactions of unsaturated fatty acids and oxides of nitrogen, are a class of endogenous anti-inflammatory mediators.