Sina Webering1, Lars Peter Lunding1, Christina Vock2, Alexandra Schröder1, Karoline I Gaede3, Christian Herzmann4, Heinz Fehrenbach2, Michael Wegmann1. 1. Division of Asthma Exacerbation & Regulation, Priority Area Asthma & Allergy, Research Center Borstel- Leibniz Lung Center, Borstel, Germany. 2. Division of Experimental Pneumology, Priority Area Asthma & Allergy, Research Center Borstel- Leibniz Lung Center, Borstel, Germany. 3. BioMaterialBank Nord, Research Center Borstel- Leibniz Lung Center, Borstel, Germany. 4. Center for Clinical Studies, Research Center Borstel- Leibniz Lung Center, Borstel, Germany.
Abstract
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.
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.
Authors: R N Khramova; E V Tush; A A Khramov; D Yu Ovsyannikov; K S Popov; I V Dolbin; O V Khaletskaya; A B Stroganov; N I Kubysheva; T I Eliseeva Journal: Sovrem Tekhnologii Med Date: 2020-06-28
Authors: Andreas Frey; Lars P Lunding; Johanna C Ehlers; Markus Weckmann; Ulrich M Zissler; Michael Wegmann Journal: Front Immunol Date: 2020-04-28 Impact factor: 7.561