Journal
CLINICAL IMMUNOLOGY
Volume 176, Issue -, Pages 94-99Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2017.01.002
Keywords
Hypoxia inducible factor (HIF)-1 alpha; Asthma; Allergic inflammation; Eosinophils; Nitric oxide; YC-1
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Funding
- BLRD VA [IK2 BX001313] Funding Source: Medline
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Hypoxia-inducible factor (HIF)-1 alpha is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-l alpha regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-l alpha inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype. Systemic treatment with HIF-la antagonist YC-1 suppressed the increase in HIF-l alpha 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-l alpha inhibition in different genetic backgrounds, and thus different AIAD phenotypes, decreases airway resistance and markers of inflammation in a background specific manner. Capsule summary: Asthma is a common disease that can be difficult to control with current therapeutics. We describe how pharmacologic targeting of a specific transcription factor, HIF-l alpha, suppresses asthmatic airway reactivity and inflammation. Published by Elsevier Inc.
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