The Expression of TRPV1 in Airway Epithelium and its Role in Airway Hypersensitivity

J.Xu^1,2, M. Ghadiri¹, B. McParland², M.Svolos¹, L.Moir¹, F.Sanai^1,2, D. Traini^1,2, P.M.Young¹

¹Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, Sydney, 2037, Australia

²The University of Sydney, Camperdown, Sydney, 2006, Australia

Summary

The transmembrane protein TRPV1 is widely associated with thermal nociception and is responsible for airway hypersensitivity and chronic cough in a neural mediated pathway. However, there is growing evidence of TRPV1 associated in lung epithelial cells resulting in airway inflammation via a direct epithelial route which paves the way for development of new antitussive targets. This study aims to quantify the distribution and localisation of TRPV1 in lung epithelial cells and determine potential up-regulatory, inflammatory and cytotoxicity effects of TRPV1 agonists including capsaicin, heat and acidity.  Capsaicin is shown to be toxic on airways in high concentrations. TRPV1 expression was steady throughout all cell lines, however variability of protein expression was found in treatments involving heat and acidity. Bronchoconstriction of TRPV1 activity is likely to deteriorate the symptoms of patients suffering from obstructive airway diseases including asthma or chronic obstructive pulmonary disease (COPD). Henceforth, it can be determined that airway epithelial injury causing acidity and heat through inflammation, can trigger changes in the airway epithelium in the chronic state.  Implications of this finding will enable the development of specific antitussive and anti-inflammatory agents on airways instead of systemic administration.