TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis.

Published

Journal Article

Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1(-/-) mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis.

Full Text

Duke Authors

Cited Authors

  • Liu, B; Escalera, J; Balakrishna, S; Fan, L; Caceres, AI; Robinson, E; Sui, A; McKay, MC; McAlexander, MA; Herrick, CA; Jordt, SE

Published Date

  • September 2013

Published In

Volume / Issue

  • 27 / 9

Start / End Page

  • 3549 - 3563

PubMed ID

  • 23722916

Pubmed Central ID

  • 23722916

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.13-229948

Language

  • eng

Conference Location

  • United States