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DOI: 10.1055/s-0036-1571990
The α-melanocyte stimulating hormone diminishes allergic airway inflammation through melanocortin receptor 5
Rationale: Originally, the α-melanocyte-stimulating hormone (α-MSH) has been described to stimulate melanine production and to diminish inflammation in the skin by binding to different melanocortin receptors (MC-R). Antiinflammatory effects have also been confirmed for several dermatologic and neurologic disorders. However, until yet, it is unknown, whether α-MSH also plays a role in the pathogenesis of chronic inflammatory diseases such as asthma and through which receptor its effects are mediated.
Methods: Wild-type and MC5-R knockout mice were sensitized to ovalbumin (OVA) and challenged with an OVA aerosol to induce acute experimental asthma. α-MSH was applied intra-tracheally, the α-MSH antibody intra-peritoneally prior each OVA Challenge. ELISA was utilized to assess α-MSH and cytokine levels in broncho-alveolar lavage (BAL) fluid. Expression of MC-Rs was analyzed by qPCR and immunohistology. Airway hyperresponsiveness (AHR) was determined by using the Buxco FinePoint RC system.
Results: In mouse models of acute and chronic experimental allergic asthma α-MSH is produced in inflamed airways and the amount of α-MSH released into the broncho-alveolar lumen increases with intensity and duration of allergic airway inflammation. Thereby, the airway epithelium appears to be the main production site of α-MSH. From the five melanocortin receptors that have been identified so far, only MC5-R is expressed in lungs of healthy animals. In contrast, animals with experimental asthma displayed not only expression of MC5-R but also of MC1-R. In these mice neutralization of α-MSH by application of a specific antibody resulted in an augmented infiltration of eosinophils into the airways, while intra-tracheal application of α-MSH significantly downregulated airway inflammation as well as AHR. These beneficial effects of α-MSH were absent in MC5-R knockout mice.
Conclusion: These data indicate that α-MSH diminishes allergic airway inflammation and AHR through MC5-R.