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

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

Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 176(2017) vom: 01. März, Seite 94-99
1. Verfasser: Dewitz, Carola (VerfasserIn)
Weitere Verfasser: McEachern, Elisa, Shin, Stephanie, Akong, Kathryn, Nagle, Dale G, Broide, David H, Akuthota, Praveen, Crotty Alexander, Laura E
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Allergic inflammation Asthma Eosinophils Hypoxia inducible factor (HIF)-1α Nitric oxide YC-1 Hypoxia-Inducible Factor 1, alpha Subunit mehr... Interleukin-13 Interleukin-5 Nitric Oxide 31C4KY9ESH Nitric Oxide Synthase Type II EC 1.14.13.39
Beschreibung
Zusammenfassung:Published by Elsevier Inc.
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
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-1α, suppresses asthmatic airway reactivity and inflammation
Beschreibung:Date Completed 05.06.2017
Date Revised 14.12.2018
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2017.01.002