The alpha-melanocyte-stimulating hormone acts as a local immune homeostasis factor in experimental allergic asthma.
animal models
asthma
epithelium
immune homeostasis
inflammation
α-MSH
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
30
11
2018
revised:
01
03
2019
accepted:
23
03
2019
pubmed:
14
4
2019
medline:
21
8
2020
entrez:
14
4
2019
Statut:
ppublish
Résumé
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. This study aimed at investigating the role and regulatory mechanisms of α-MSH in asthma pathogenesis. 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. 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. α-MSH acts as a regulatory factor to maintain local immune homeostasis in allergic bronchial asthma.
Sections du résumé
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.
Substances chimiques
alpha-MSH
581-05-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1026-1039Informations de copyright
© 2019 John Wiley & Sons Ltd.