"Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness?
Abstract
We propose that the respiratory symptoms of subjects with GWI is caused in part by enhanced airway sensitivity to irritants, mediated primarily by upregulated or sensitized TRP channels in the airway. We have now shown that transformed and primary airway epithelial cells express functional TRPV1. More recently we found that these cells also express another important irritant receptor, namely TRPA1. Activation of either TRPV1 or TRPA1 results in increased expression of both the inflammatory cytokine IL-8 and the neurotrophin NGF in airway epithelial cells. We have further shown that NGF as well as bradykinin and CCL5 can sensitize TRPV1, lower the activation threshold, and enhance the inflammatory consequences of agonist stimulation. The combination of sensitized TRPV1 channels that have a lower threshold for activation from common irritants combined with TRP activation-mediated synthesis of NGF leading to further sensitization of sensory afferents and epithelial cells suggests a mechanism by which non-specific airway sensitivity may be initiated and sustained in a self-perpetuating manner.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2010
- Accession Number
- ADA536752
Entities
People
- Bruce L. Zuraw