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Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin.

ABSTRACT: Glucagon has been shown to be beneficial as a treatment for bronchospasm in asthmatics. Here, we investigate if glucagon would prevent airway hyperreactivity (AHR), lung inflammation, and remodeling in a murine model of asthma. Glucagon (10 and 100?µg/Kg, i.n.) significantly prevented AHR and eosinophilia in BAL and peribronchiolar region induced by ovalbumin (OVA) challenge, while only the dose of 100?µg/Kg of glucagon inhibited subepithelial fibrosis and T lymphocytes accumulation in BAL and lung. The inhibitory action of glucagon occurred in parallel with reduction of OVA-induced generation of IL-4, IL-5, IL-13, TNF-?, eotaxin-1/CCL11, and eotaxin-2/CCL24 but not MDC/CCL22 and TARC/CCL17. The inhibitory effect of glucagon (100?µg/Kg, i.n.) on OVA-induced AHR and collagen deposition was reversed by pre-treatment with indomethacin (10?mg/Kg, i.p.). Glucagon increased intracellular cAMP levels and inhibits anti-CD3 plus anti-CD28-induced proliferation and production of IL-2, IL-4, IL-10, and TNF- ? from TCD4⁺ cells in vitro. These findings suggest that glucagon reduces crucial features of asthma, including AHR, lung inflammation, and remodeling, in a mechanism probably associated with inhibition of eosinophils accumulation and TCD4⁺ cell proliferation and function. Glucagon should be further investigated as an option for asthma therapy.

SUBMITTER: Insuela DBR

PROVIDER: S-EPMC6482309 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin.

Insuela Daniella B R DBR Azevedo Carolina T CT Coutinho Diego S DS Magalhães Nathalia S NS Ferrero Maximiliano R MR Ferreira Tatiana Paula T TPT Cascabulho Cynthia M CM Henriques-Pons Andrea A Olsen Priscilla C PC Diaz Bruno L BL Silva Patricia M R PMR Cordeiro Renato S B RSB Martins Marco A MA Carvalho Vinicius F VF

Scientific reports 20190424 1

Glucagon has been shown to be beneficial as a treatment for bronchospasm in asthmatics. Here, we investigate if glucagon would prevent airway hyperreactivity (AHR), lung inflammation, and remodeling in a murine model of asthma. Glucagon (10 and 100 µg/Kg, i.n.) significantly prevented AHR and eosinophilia in BAL and peribronchiolar region induced by ovalbumin (OVA) challenge, while only the dose of 100 µg/Kg of glucagon inhibited subepithelial fibrosis and T lymphocytes accumulation in BAL and l ...[more]

PMID: 31019244

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Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin.

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Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin.

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