Role of TRPV1 in Airway Hypersensitivity Induced by Inflammation

Summary

Principal Investigator: Lu Yuan Lee
Abstract: Airway hypersensitivity, characterized by exaggerated sensory and reflexogenic responses to inhaled irritants, is a prominent pathophysiological feature of various airway inflammatory diseases (e.g., asthma, bronchitis, etc). Increasing and compelling evidence indicates that vagal bronchopulmonary C-fibers play a pivotal role in the manifestation of airway hypersensitivity. Recent investigations further suggest that the TRPV1 receptor, a non-selective cation channel and a polymodal transducer selectively expressed in C-fiber afferents, is likely involved in the airway hypersensitivity generated by airway inflammatory reaction. Indeed, a recent study in our lab has demonstrated that allergen sensitization-induced airway inflammation markedly enhanced the sensitivity of pulmonary C-fiber afferents and, more importantly, induced TRPV1 expression in myelinated pulmonary afferents that normally do not exhibit any capsaicin sensitivity. However, the physiological implication and the mechanism underlying the TRPV1 over- expression during airway inflammation are yet not fully understood. In this proposal, a research plan is designed to characterize the role of TRPV1 in the development of airway hypersensitivity when chronic airway inflammation is induced by allergen sensitization. Our hypothesis is that the enhanced airway sensitivity results from a combination of increased expression and excitability of this channel in the vagal bronchopulmonary sensory terminals. We further hypothesize that tumor necrosis factor 1, a pro-inflammatory cytokine and known to be released in the lung during allergic airway inflammation, is an important contributor to the over-expression of TRPV1 in these sensory neurons. Results obtained from these studies should provide important information about the mechanism that up-regulates the expression and excitability of the TRPV1 channel in the airway sensory neurons, and bring a new insight into the pathogenesis and therapeutic strategy for alleviating the airway hypersensitivity caused by allergic airway inflammation. PUBLIC HEALTH RELEVANCE: In airway inflammatory diseases such as asthma and bronchitis, the respiratory tract becomes overly sensitive to inhaled irritants. This research proposal is designed to test our hypothesis that a specific ion channel, namely TRPV1, plays a major role in the exceedingly high excitability of airway sensory nerves caused by allergic inflammation. The results obtained from these studies should bring a new insight into the pathogenesis and therapeutic strategy for alleviating the airway hypersensitivity.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Breathing hot humid air induces airway irritation and cough in patients with allergic rhinitis
    Mehdi Khosravi
    Department of Internal Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY, 40536, United States
    Respir Physiol Neurobiol 198:13-9. 2014
  2. ncbi Sensory nerves in lung and airways
    Lu Yuan Lee
    Department of Physiology, University of Kentucky, Lexington, Kentucky
    Compr Physiol 4:287-324. 2014
  3. pmc Bronchoconstriction induced by increasing airway temperature in ovalbumin-sensitized rats: role of tachykinins
    Chun Chun Hsu
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
    J Appl Physiol (1985) 115:688-96. 2013
  4. pmc Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors
    Chun Chun Hsu
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
    Am J Physiol Regul Integr Comp Physiol 305:R769-79. 2013
  5. pmc Pulmonary chemoreflex responses are potentiated by tumor necrosis factor-alpha in mice
    Ruei Lung Lin
    Department of Physiology, University of Kentucky, Lexington, Kentucky 40536 0298, USA
    J Appl Physiol (1985) 114:1536-43. 2013
  6. pmc Acid-sensing by airway afferent nerves
    Lu Yuan Lee
    Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536 0298, USA
    Pulm Pharmacol Ther 26:491-7. 2013
  7. pmc House dust mite potentiates capsaicin-evoked Ca2+ transients in mouse pulmonary sensory neurons via activation of protease-activated receptor-2
    Qihai Gu
    Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA
    Exp Physiol 97:534-43. 2012
  8. pmc Bronchoconstriction triggered by breathing hot humid air in patients with asthma: role of cholinergic reflex
    Don Hayes
    Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA
    Am J Respir Crit Care Med 185:1190-6. 2012
  9. pmc Airway irritation and cough evoked by acid: from human to ion channel
    Qihai Gu
    Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA
    Curr Opin Pharmacol 11:238-47. 2011
  10. ncbi TRPV1 as a cough sensor and its temperature-sensitive properties
    Lu Yuan Lee
    Department of Physiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536 0298, USA
    Pulm Pharmacol Ther 24:280-5. 2011

Scientific Experts

  • Lu Yuan Lee
  • Ruei Lung Lin
  • Qihai Gu
  • Chun Chun Hsu
  • Mehdi Khosravi
  • Don Hayes
  • Paul B Collins
  • You Shuei Lin
  • Richard Kryscio
  • Youmin Hu
  • Jaclyn A Smith
  • Marcus J Geer
  • Yu Jung Lin

Detail Information

Publications11

  1. pmc Breathing hot humid air induces airway irritation and cough in patients with allergic rhinitis
    Mehdi Khosravi
    Department of Internal Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY, 40536, United States
    Respir Physiol Neurobiol 198:13-9. 2014
    ..In conclusion, hyperventilation of HA triggered vigorous cough response and throat irritation in AR patients, indicating the involvement of sensory nerves innervating upper airways. ..
  2. ncbi Sensory nerves in lung and airways
    Lu Yuan Lee
    Department of Physiology, University of Kentucky, Lexington, Kentucky
    Compr Physiol 4:287-324. 2014
    ..Several important and challenging questions regarding these sensory nerves are discussed. Searching for these answers will be a critical step in developing the translational research and effective treatments of airway diseases...
  3. pmc Bronchoconstriction induced by increasing airway temperature in ovalbumin-sensitized rats: role of tachykinins
    Chun Chun Hsu
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
    J Appl Physiol (1985) 115:688-96. 2013
    ....
  4. pmc Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors
    Chun Chun Hsu
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
    Am J Physiol Regul Integr Comp Physiol 305:R769-79. 2013
    ....
  5. pmc Pulmonary chemoreflex responses are potentiated by tumor necrosis factor-alpha in mice
    Ruei Lung Lin
    Department of Physiology, University of Kentucky, Lexington, Kentucky 40536 0298, USA
    J Appl Physiol (1985) 114:1536-43. 2013
    ..In conclusion, TNF-α pretreatment induced airway inflammation and a sustained elevation of pulmonary chemoreflex sensitivity, which was mediated through an activation of both types of TNF receptors...
  6. pmc Acid-sensing by airway afferent nerves
    Lu Yuan Lee
    Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536 0298, USA
    Pulm Pharmacol Ther 26:491-7. 2013
    ....
  7. pmc House dust mite potentiates capsaicin-evoked Ca2+ transients in mouse pulmonary sensory neurons via activation of protease-activated receptor-2
    Qihai Gu
    Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA
    Exp Physiol 97:534-43. 2012
    ....
  8. pmc Bronchoconstriction triggered by breathing hot humid air in patients with asthma: role of cholinergic reflex
    Don Hayes
    Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA
    Am J Respir Crit Care Med 185:1190-6. 2012
    ..Recent studies showed that an increase in temperature activates vagal bronchopulmonary C-fiber sensory nerves, which upon activation can elicit reflex bronchoconstriction...
  9. pmc Airway irritation and cough evoked by acid: from human to ion channel
    Qihai Gu
    Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA
    Curr Opin Pharmacol 11:238-47. 2011
    ....
  10. ncbi TRPV1 as a cough sensor and its temperature-sensitive properties
    Lu Yuan Lee
    Department of Physiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536 0298, USA
    Pulm Pharmacol Ther 24:280-5. 2011
    ....
  11. pmc Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-{alpha} in rat pulmonary sensory neurons
    Youmin Hu
    Dept of Physiology, Univ of Kentucky, Lexington, USA
    Am J Physiol Lung Cell Mol Physiol 299:L483-92. 2010
    ..This action of TNFα may contribute in part to the airway hyperresponsiveness induced by this cytokine...