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

Jalahalli M. Siddesha, Emily M. Nakada, Bethany R. Mihavics, Sidra M. Hoffman, Gurkiranjit K. Rattu, Nicolas Chamberlain, Jonathon M. Cahoon, Karolyn G. Lahue, Nirav Daphtary, Minara Aliyeva, David G. Chapman, Dhimant H. Desai, Matthew E. Poynter, Vikas Anathy

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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, methacholineinduced 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.

Original languageEnglish (US)
Pages (from-to)L1243-L1259
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number11
DOIs
StatePublished - Jun 1 2016

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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