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Hypoxia-inducible factor-1α inhibition modulates airway hyperresponsiveness and nitric oxide levels in a BALB/c mouse model of asthma

Item Type:Article
Title:Hypoxia-inducible factor-1α inhibition modulates airway hyperresponsiveness and nitric oxide levels in a BALB/c mouse model of asthma
Creators Name:Dewitz, C. and McEachern, E. and Shin, S. and Akong, K. and Nagle, D.G. and Broide, D.H. and Akuthota, P. and Crotty Alexander, L.E.
Abstract:Hypoxia inducible factor (HIF)-1α is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-1α regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-1α inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype. Systemic treatment with HIF-1α antagonist YC-1 suppressed the increase in HIF-1α expression seen in control AIAD mice. Treatment with YC-1 also decreased AHR, blood eosinophilia, and allergic inflammatory gene expression: IL-5, IL-13, myeloperoxidase and iNOS. AIAD mice had elevated BAL levels of NO, and treatment with YC-1 eliminated this response. However, YC-1 did not decrease BAL, lung or bone marrow eosinophilia. We conclude that HIF-1α inhibition in different genetic backgrounds, and thus different AIAD phenotypes, decreases airway resistance and markers of inflammation in a background specific manner.
Keywords:Hypoxia Inducible Factor (HIF)-1α, Asthma, Allergic Inflammation, Easoinophils, Nitric Oxide, YC-1, Animals, Mice
Source:Clinical Immunology
ISSN:1521-6616
Publisher:Elsevier / Academic Press (U.S.A.)
Volume:176
Page Range:94-99
Date:March 2017
Official Publication:https://doi.org/10.1016/j.clim.2017.01.002
PubMed:View item in PubMed

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