Date of Completion

2016

Document Type

Honors College Thesis

Department

Department of Biology; Department of Pathology and Laboratory Medicine

Thesis Type

Honors College, College of Arts and Science Honors

First Advisor

Dr. Vikas Anathy

Second Advisor

Dr. Brent Lockwood

Keywords

allergic airway inflammation, asthma, ER stress, immunohistochemistry, TUDCA, periodic-acid schiff

Abstract

Asthma is a chronic inflammatory disease characterized by increased airway inflammation and fibrosis. So far, endoplasmic reticulum (ER) stress has been shown to play a role in several inflammatory diseases, however, its involvement in the pathogenesis of allergic asthma has not been clearly understood. It is also known that ER stress inhibitor chemical chaperone tauroursodeoxycholic acid (TUDCA) has been shown to attenuate inflammation in obese and diabetic conditions, but its therapeutic potential in allergic asthma is currently unknown. The current study was designed to investigate the role of ER stress in house dust mite (HDM)-induced allergic asthma, and the therapeutic efficacy of TUDCA in attenuating the hallmarks of allergic asthma (airway inflammation, mucus metaplasia and fibrosis), using a mouse model of HDM-induced allergic airways disease. Inflammation was measured by inflammatory cell counts (cell differentials) and cytokine analyses (ELISA). ER stress was examined by the expression levels of ER stress markers ATF6, ERp57, GRP78, GRP94, and CHOP. Further, changes in the airways to indicate fibrosis was determined by quantifying alpha-smooth muscle actin (α-SMA) cell expression and hydroxyproline content in the lungs. TUDCA administered during the HDM-challenge phase (as a prophylactic), significantly decreased inflammatory cells and cytokines, ER stress markers, peri-bronchial collagen content and α-SMA cell expression. Moreover, TUDCA administered after the HDM-challenge phase (as a therapeutic), markedly decreased HDM-induced airway inflammation, ER stress makers, but not airway remodeling. These results suggest that the inhibition of ER stress by a chemical chaperone, TUDCA, could be helpful in the treatment of asthmatic patients.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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