title: Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.
abstract: BACKGROUND
  Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO2-FAs), such as nitro oleic acid (OA-NO2) and nitro linoleic acid (LNO2). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO2-FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO2, an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation.
  
  
  METHODS
  We evaluated the effect of OA-NO2on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten.
  
  
  RESULTS
  We found that subcutaneous (SC) OA-NO2injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO2significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO2is capable of enhancing regulatory T-cell activity. Thus, OA-NO2treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses.
  
  
  CONCLUSIONS
  Overall, these results support the development of OA-NO2as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases.
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: A R
authors.identifier: http://orcid.org/0000-0001-6931-8605
authors.initials: AR
authors.lastname: Mathers
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Carey
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Killeen
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Diaz-Perez
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Salvatore
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Schopfer
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Freeman
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Falo
mesh_terms: D000818:Animals; D015415:Biomarkers; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D009573:Nitrites; D009569:Nitric Oxide
keywords: T regulatory cells; allergic contact dermatitis; contact hypersensitivity; electrophilic fatty acids; nitro-oleic acid