Role of hypoxia-inducible factor 1{alpha} in modulating cobalt-induced lung inflammation.

American Journal of Physiology. Lung Cellular and Molecular Physiology
Yogesh SainiJ J LaPres

Abstract

Hypoxia plays an important role in development, cellular homeostasis, and pathological conditions, such as cancer and stroke. There is also growing evidence that hypoxia is an important modulator of the inflammatory process. Hypoxia-inducible factors (HIFs) are a family of proteins that regulate the cellular response to oxygen deficit, and loss of HIFs impairs inflammatory cell function. There is little known, however, about the role of epithelial-derived HIF signaling in modulating inflammation. Cobalt is capable of eliciting an allergic response and promoting HIF signaling. To characterize the inflammatory function of epithelial-derived HIF in response to inhaled cobalt, a conditional lung-specific HIF1alpha, the most ubiquitously expressed HIF, deletion mouse, was created. Control mice showed classic signs of metal-induced injury following cobalt exposure, including fibrosis and neutrophil infiltration. In contrast, HIF1alpha-deficient mice displayed a Th2 response that resembled asthma, including increased eosinophilic infiltration, mucus cell metaplasia, and chitinase-like protein expression. The results suggest that epithelial-derived HIF signaling has a critical role in establishing a tissue's inflammatory response, and ...Continue Reading

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Citations

Feb 27, 2013·Omics : a Journal of Integrative Biology·Juan-juan FuPeter G Gibson
Jun 1, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yogesh SainiJohn J LaPres
Nov 20, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Song GaoWande Li
Dec 20, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Krista K GreenwoodJohn J LaPres
Feb 9, 2012·American Journal of Respiratory Cell and Molecular Biology·Tanveer AhmadAnurag Agrawal
Nov 13, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Steven P ProperJohn J Lapres
May 27, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Barbara L F KaplanPeer W F Karmaus
Sep 12, 2018·Critical Reviews in Toxicology·D LisonG Van Maele-Fabry
Sep 20, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nels OlsonAlbert van der Vliet
Jul 30, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hung-Chang TsuiJeroen A J Vanoirbeek
Sep 20, 2017·Particle and Fibre Toxicology·Rong WanQunwei Zhang
Feb 11, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Atish GhewareBhavana Prasher
Oct 15, 2011·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Olga I KubrakVolodymyr I Lushchak

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