Decreased Ovalbumin-Induced Airway Inflammation in Mice Deficient in the Sensory Neuronal Ion Channel TRPA1.

Abstract

The airways are densely innervated by peripheral sensory neurons. Activation of chemosensory C‐fibers by chemical irritants triggers defensive reflexes such as cough and sneezing, and initiates airway constriction and glandular fluid secretion. Local neuronal release of pro‐inflammatory peptides promotes edema formation and vascular leakage. We recently identified TRPA1 as the chemosensory receptor for noxious oxidants and electrophiles in the airways. Chemosensory neurons are activated or sensitized during chronic inflammatory states and may be involved in the initiation and maintenance of airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Inflammatory mediators, including prostaglandins, bradykinin, histamine, reactive oxygen species and lipid peroxidation products activate or sensitize TRPA1 and other sensory ion channels such as TRPV1, the capsaicin receptor. We asked whether absence of TRPA1 or TRPV1 would affect the inflammatory process in the ovalbumin (OVA) mouse model of allergic airway inflammation. OVA‐challenged TRPA1‐deficient mice showed dramatically diminished eosinophil infiltration in the airways. Multiplex analysis of bronchoalveolar lavage fluid showed a reduction in levels of Th2‐derived cytokines and chemokines. We conclude that neuronal TRPA1 channels are essential for establishment of OVA‐dependent airway inflammation in mice.