Effect of a chemical chaperone, tauroursodeoxycholic acid, on HDM-induced allergic airway disease.

Autor:	Siddesha JM; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Nakada EM; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Mihavics BR; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Hoffman SM; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Rattu GK; Department of Biology, University of Vermont, Burlington, Vermont;, Chamberlain N; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Cahoon JM; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Lahue KG; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Daphtary N; Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Aliyeva M; Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Chapman DG; Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont; Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia; and., Desai DH; Department of Pharmacology, Penn State Hershey College of Medicine, Hershey, Pensylvania., Poynter ME; Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont;, Anathy V; Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont; vikas.anathy@med.uvm.edu.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2016 Jun 01; Vol. 310 (11), pp. L1243-59. Date of Electronic Publication: 2016 May 06.
DOI:	10.1152/ajplung.00396.2015
Abstrakt:	Endoplasmic reticulum (ER) stress-induced unfolded protein response plays a critical role in inflammatory diseases, including allergic airway disease. However, the benefits of inhibiting ER stress in the treatment of allergic airway disease are not well known. Herein, we tested the therapeutic potential of a chemical chaperone, tauroursodeoxycholic acid (TUDCA), in combating allergic asthma, using a mouse model of house dust mite (HDM)-induced allergic airway disease. TUDCA was administered during the HDM-challenge phase (preventive regimen), after the HDM-challenge phase (therapeutic regimen), or therapeutically during a subsequent HDM rechallenge (rechallenge regimen). In the preventive regimen, TUDCA significantly decreased HDM-induced inflammation, markers of ER stress, airway hyperresponsiveness (AHR), and fibrosis. Similarly, in the therapeutic regimen, TUDCA administration efficiently decreased HDM-induced airway inflammation, mucus metaplasia, ER stress markers, and AHR, but not airway remodeling. Interestingly, TUDCA administered therapeutically in the HDM rechallenge regimen markedly attenuated HDM-induced airway inflammation, mucus metaplasia, ER stress markers, methacholine-induced AHR, and airway fibrotic remodeling. These results indicate that the inhibition of ER stress in the lungs through the administration of chemical chaperones could be a valuable strategy in the treatment of allergic airway diseases. (Copyright © 2016 the American Physiological Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu