Date of Award

January 2011

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Sven E. Jordt

Subject Area(s)

Pharmacology

Abstract

Asthma results from exposure to allergens and other airway irritants. While clinical treatment of the disease has recently expanded beyond simply β-agonists and inhaled steroids, recent strategies seeking to modulate the immune mechanisms of the disease have offered incomplete control of the disease. This study demonstrates a mechanistically novel component in the development of asthmatic inflammation mediated by sensory neurons within the lung parenchyma. Sensory neurons are rich in the transient receptor potential channel A1 (TRPA1), an ion channel activated by strong triggers of asthma, including cigarette smoke, chlorine, and hypochlorite. This project examines the role of TRPA1 in the development of allergic inflammation in an ovalbumin-based murine model of asthma. All quantifiable measures of asthmatic inflammation including airway hyperreactivity, mucus production, and cytokine production were significantly reduced by both genetic deletion and pharmacological blockade of TRPA1. This finding suggests not only that TRPA1 is a mechanistically important factor in the development of allergic inflammation, but it also offers a new potential pharmacological target in the treatment of asthma.

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