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TRPA1 acts in a protective manner in imiquimod-induced psoriasiform dermatitis in mice

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Ágnes Kemény, Xenia Kodji, Szabina Horváth, Rita Komlódi, Éva Szőke, Zoltán Sándor, Anikó Perkecz, Csaba Gyömörei, György Sétáló, Balázs Kelemen, Tamás Bíró, Balázs István Tóth, Susan D. Brain, Erika Pintér, Rolland Gyulai

Original languageEnglish
Pages (from-to)1774-1784
Number of pages11
JournalJournal of Investigative Dermatology
Volume138
Issue number8
Early online date14 Mar 2018
DOIs
Accepted/In press18 Feb 2018
E-pub ahead of print14 Mar 2018
Published14 Mar 2018

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Abstract

The present study revealed the modulatory role of Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) cation channels in Aldara-induced (5% imiquimod, IMQ) murine psoriasis model using selective antagonists and genetically altered animals. We have also developed a refined localized model to enable internal controls and reduce systemic effects. Skin pathology was quantified by measuring skin thickness, scaling, blood flow and analyzing dermal cellular infiltrate, while nocifensive behaviours were also observed. Cytokine gene expression profiles were measured ex vivo. Psoriasiform dermatitis was significantly enhanced in TRPA1 KO mice and with TRPA1 antagonist (A967079) treatment. By comparison, symptoms were decreased when TRPV1 function was inhibited. IMQ induced Ca2+ influx in TRPA1-, but not in TRPV1-expressing cell lines. Immunohistochemical studies revealed that CD4+ T helper cells express TRPA1 but not TRPV1 ion channels in mice skin. Compared to the TRPV1 KO animals, additional elimination of the TRPA1 channels in the TRPV1/TRPA1 double KO mice did not modify the outcome of the IMQ-induced reaction, further supporting the dominant role of TRPV1 in the process. Our results suggest that the protective effects in psoriasiform dermatitis can be mediated by the activation of neuronal and non-neuronal TRPA1 receptors.

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