title: Effect of a chemical chaperone, tauroursodeoxycholic acid, on HDM-induced allergic airway disease.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Jalahalli M
authors.initials: JM
authors.lastname: Siddesha
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Emily M
authors.initials: EM
authors.lastname: Nakada
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Bethany R
authors.initials: BR
authors.lastname: Mihavics
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Sidra M
authors.initials: SM
authors.lastname: Hoffman
authors.affiliation: Department of Biology, University of Vermont, Burlington, Vermont;
authors.forename: Gurkiranjit K
authors.initials: GK
authors.lastname: Rattu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chamberlain
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Jonathon M
authors.initials: JM
authors.lastname: Cahoon
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Karolyn G
authors.initials: KG
authors.lastname: Lahue
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Nirav
authors.initials: N
authors.lastname: Daphtary
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Minara
authors.initials: M
authors.lastname: Aliyeva
authors.affiliation: 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.
authors.forename: David G
authors.initials: DG
authors.lastname: Chapman
authors.affiliation: Department of Pharmacology, Penn State Hershey College of Medicine, Hershey, Pensylvania.
authors.forename: Dhimant H
authors.initials: DH
authors.lastname: Desai
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont; vikas.anathy@med.uvm.edu.
authors.forename: Vikas
authors.initials: V
authors.lastname: Anathy
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000276:immunology; D005260:Female; D008810:Mice, Inbred C57BL; D039981:Pyroglyphidae / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine
keywords: ER stress; airway hyperresponsiveness; asthma; house dust mite; inflammation