Electrophilic nitro‐fatty acids suppress allergic contact dermatitis in mice

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.