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The alpha-melanocyte-stimulating hormone acts as a local immune homeostasis factor in experimental allergic asthma
Sina Webering1, Lars Peter Lunding1, Christina Vock2
1Division of Asthma Exacerbation & Regulation, Priority Area Asthma & Allergy, Research Center Borstel- Leibniz Lung Center, Borstel, Germany.
Background:
Originally, the neuropeptide α-melanocyte-stimulating hormone (α-MSH) has been described as a mediator of skin pigmentation. However, recent studies have shown that α-MSH is able to modulate inflammation in various tissues including the lung. So far, it is still not clear whether α-MSH also plays a role in allergic bronchial asthma.
Objective:
This study aimed at investigating the role and regulatory mechanisms of α-MSH in asthma pathogenesis.
Methods:
α-MSH levels were measured in bronchoalveolar lavage (BAL) fluid of asthmatic and non-asthmatic individuals as well as of healthy mice and mice with experimental asthma. Wild-type mice were sensitized to ovalbumin (OVA) and exposed to an OVA aerosol in order to induce experimental allergic asthma. α-MSH was administrated intratracheally, the α-MSH antibody intraperitoneally prior each OVA challenge. Airway inflammation, cytokine production, mucus production, airway hyperresponsiveness and receptor expression were assessed.
Results:
α-MSH levels in BAL of asthmatic individuals and mice were significantly higher compared to healthy controls. In a mouse model of experimental asthma, α-MSH neutralization increased airway inflammation and mucus production, whereas local administration of α-MSH significantly reduced inflammation of the airways. The beneficial effects were further associated with decreased levels of eosinophilic chemoattractant factors that are released by MC5R-positive T helper 2 and airway epithelial cells.
Conclusion And Clinical Relevance:
α-MSH acts as a regulatory factor to maintain local immune homeostasis in allergic bronchial asthma.
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