title: TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USA.
authors.forename: Boyi
authors.initials: B
authors.lastname: Liu
authors.forename: Jasmine
authors.initials: J
authors.lastname: Escalera
authors.forename: Shrilatha
authors.initials: S
authors.lastname: Balakrishna
authors.forename: Lu
authors.initials: L
authors.lastname: Fan
authors.forename: Ana I
authors.initials: AI
authors.lastname: Caceres
authors.forename: Eve
authors.initials: E
authors.lastname: Robinson
authors.forename: Aiwei
authors.initials: A
authors.lastname: Sui
authors.forename: M Craig
authors.initials: MC
authors.lastname: McKay
authors.forename: M Allen
authors.initials: MA
authors.lastname: McAlexander
authors.forename: Christina A
authors.initials: CA
authors.lastname: Herrick
authors.forename: Sven E
authors.initials: SE
authors.lastname: Jordt
mesh_terms: D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone / Q000633:toxicity; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D010081:Oxazolone
keywords: TRP channels; pruritis; sensory neurons