Topical electrophilic nitro-fatty acids potentiate cutaneous immune responses. (MUC7P.775)

Abstract

Abstract Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. In this regard, there is considerable interest in employing nitro-fatty acids and other electrophilic fatty acids for the prevention and treatment of inflammatory disorders. We evaluated nitro-oleic acid (OA-NO2) in a preclinical murine model of allergic contact dermatitis (ACD) as a potential topical therapy for the treatment of ACD. In marked contrast to previous findings, topical OA-NO2 potentiated hapten-dependent inflammation inducing a sustained psoriasis-like inflammatory response characterized by psoriasiform histological features, increased angiogenesis, and an inflammatory infiltrate that included neutrophils, inflammatory monocytes, and γδ T cells. Interestingly, analysis by HPLC-MS-MS of skin from psoriasis patients revealed a significant increase in nitro-fatty acids in lesional skin compared to non-lesional skin. Overall, when applied topically to the cutaneous microenvironment nitro-fatty acids can potentiate inflammatory responses. Thus, it is paramount that a better understanding be obtained of how electrophilic fatty acid derivatives regulate cutaneous immunity due to the widespread use of fatty acids in topical creams and the abundant formation of electrophilic nitro-fatty acids during inflammation.