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Electrophilic nitro‐fatty acids suppress allergic contact dermatitis in mice
Author(s) -
Mathers A. R.,
Carey C. D.,
Killeen M. E.,
DiazPerez J. A.,
Salvatore S. R.,
Schopfer F. J.,
Freeman B. A.,
Falo L. D.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13067
Subject(s) - nitric oxide , sensitization , linoleic acid , pharmacology , chemistry , allergic contact dermatitis , inflammation , medicine , fatty acid , immune system , unsaturated fatty acid , immunology , allergy , biochemistry
Background Reactions between nitric oxide ( NO ), nitrite ( NO 2 − ), and unsaturated fatty acids give rise to electrophilic nitro‐fatty acids ( NO 2 ‐ FA s), such as nitro oleic acid ( OA ‐ NO 2 ) and nitro linoleic acid ( LNO 2 ). Endogenous electrophilic fatty acids ( EFA s) mediate anti‐inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 ‐ FA s and other EFA s for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA ‐ NO 2 , an exemplary nitro‐fatty acid, has the capacity to inhibit cutaneous inflammation. Methods We evaluated the effect of OA ‐ NO 2 on 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 ‐ NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA ‐ NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA ‐ NO 2 is capable of enhancing regulatory T‐cell activity. Thus, OA ‐ NO 2 treatment results in anti‐inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Conclusion Overall, these results support the development of OA ‐ NO 2 as 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.