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

Am J Physiol Lung Cell Mol Physiol. 2016 Jun 1;310(11):L1243-59. doi: 10.1152/ajplung.00396.2015. Epub 2016 May 6.


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.

Keywords: ER stress; airway hyperresponsiveness; asthma; house dust mite; inflammation.

MeSH terms

  • Airway Remodeling / drug effects
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy*
  • Asthma / immunology
  • Drug Evaluation, Preclinical
  • Endoplasmic Reticulum Stress / drug effects
  • Endoplasmic Reticulum Stress / immunology
  • Female
  • Mice, Inbred C57BL
  • Pyroglyphidae / immunology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Taurochenodeoxycholic Acid / pharmacology*
  • Taurochenodeoxycholic Acid / therapeutic use


  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine