Neutrophils induce smooth muscle hyperplasia via neutrophil elastase-induced FGF-2 in a mouse model of asthma with mixed inflammation

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
Hirohisa OgawaKoichi Tsuneyama

Abstract

Bronchial asthma is traditionally characterized by chronic allergic inflammation, including eosinophilia and elevated Th2 cytokines. Recently, IL-17-derived neutrophil infiltration was shown to correlate with asthma severity and airway remodelling. To investigate the role of IL-17-derived neutrophils in airway remodelling in chronic bronchial asthma. We utilized house dust mite antigen-induced mouse models of asthma. Intranasal sensitization and chronic antigen challenge caused a mixed allergic inflammation that included eosinophils and neutrophils (Mix-in group). We neutralized IL-17 and fibroblast growth factor (FGF-2) and investigated the mechanism of airway remodelling in the Mix-in group. The Mix-in group displayed neutrophilic infiltration and high levels of IL-17 in lung tissue. The Mix-in group also exhibited more bronchial smooth muscle hyperplasia. IL-17 neutralization decreased the magnitude of all of these effects in the Mix-in group. Antibody arrays revealed an increase in FGF-2 in the Mix-in Group relative to the Eo-ip group, and FGF-2 elevation was associated with smooth muscle hypertrophy/hyperplasia. High concentrations of neutrophil elastase enhanced E-cadherin/β-catenin signalling in bronchial epithelial cell...Continue Reading

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Citations

Jan 26, 2020·International Journal of Molecular Sciences·Lei FangMichael Roth
Apr 18, 2020·Frontiers in Cell and Developmental Biology·Yuanyang TanYan Yan
Sep 20, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leon A SokulskyPaul S Foster
Oct 14, 2020·Biochemistry. Biokhimii︠a︡·I P ShilovskiyM R Khaitov

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