Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

Background α-melanocyte-stimulating hormone (α- MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. Objective This study aims to extend our current knowledge on the melanocortin 1 receptor ( MC1R) expression in nasal tissue of patients with allergic rhinitis ( AR) and functional effects of α- MSH in human basophils especially from patients with allergic rhinitis. Methods MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α- MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. Results We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α- MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. Conclusions and Clinical Relevance MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α- MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response. [ABSTRACT FROM AUTHOR]