title: Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators.
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-gamma activation, or induction of heme oxygenase-1 expression. The electrophilic nature of fatty acid nitroalkene derivatives resulted in alkylation of recombinant NF-kappaB 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-kappaB-dependent target gene expression. Moreover, nitroalkenes inhibited endothelial tumor necrosis factor-alpha-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.
authors.affiliation: Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
authors.forename: Taixing
authors.initials: T
authors.lastname: Cui
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Paul R S
authors.initials: PR
authors.lastname: Baker
authors.forename: Carlos
authors.initials: C
authors.lastname: Batthyany
authors.forename: Balu K
authors.initials: BK
authors.lastname: Chacko
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.forename: Yuqing E
authors.initials: YE
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D047495:PPAR gamma / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D016328:NF-kappa B; D047495:PPAR gamma; D011994:Recombinant Proteins; D006419:Heme Oxygenase (Decyclizing); D009584:Nitrogen