Role of TRPA1 receptors in skin inflammation induced by volatile chemical irritants in mice

• Published in: European journal of pharmacology Vol. 858; p. 172460
• Main Authors: Norões, Maíra Macedo, Santos, Larissa Gonzaga, Gavioli, Elaine Cristina, de Paula Soares Rachetti, Vanessa, Otuki, Michel Fleith, de Almeida Cabrini, Daniela, da Silveira Prudente, Arthur, Oliveira, Janiana Raíza Jentsch Matias, de Carvalho Gonçalves, Muryel, Ferreira, Juliano, Preti, Delia, De Logu, Francesco, Nassini, Romina, André, Eunice
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-09-2019
• Subjects: Animals; Chemical irritants; Edema - chemically induced; Edema - genetics; Edema - metabolism; Edema - pathology; Gene Knockout Techniques; Inflammation - chemically induced; Inflammation - metabolism; Inflammatory skin disease; Irritant contact dermatitis; Mice; Mice, Inbred C57BL; Nociception - drug effects; Skin - drug effects; Toluene - pharmacology; Transient receptor potential ankyrin 1; TRPA1 Cation Channel - antagonists & inhibitors; TRPA1 Cation Channel - deficiency; TRPA1 Cation Channel - genetics; TRPA1 Cation Channel - metabolism; Volatilization; Xylenes - pharmacology; Chemical irritants; Inflammatory skin disease; Irritant contact dermatitis; Transient receptor potential ankyrin 1
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2019.172460

Contact dermatitis is a very common inflammatory reaction in the skin, causing not only aesthetic problems but also loss functionality at work. The molecular mechanisms of contact dermatitis induced by chemical irritants are still unclear. Considering that transient receptor potential channels (TRP) may induce neurogenic inflammation and the exacerbation of inflammatory responses, here we investigated the role of transient receptor potential channel ankyrin type-1 (TRPA1) in skin inflammation evoked by chemical irritants. Ear oedema and nociceptive responses elicited by the topical application of xylene and toluene were measured in Swiss mice, wild type and TRPA1 knockout (Trpa1−/−) C57BL/6 mice. Histological analyses were performed in mice subjected to the ear oedema assay. Topical application of xylene and toluene in the mouse ear induced an edematogenic response (0.113 ± 0.008 mm and 0.067 ± 0.011 mm), compared to vehicle (0.008 ± 0.008 mm), assessed by ear thickness measurements and histological analyses. These responses were prevented by topical pretreatment with a selective TRPA1 antagonist, HC-030031 (% inhibition: xylene 36.8 ± 9.4% and toluene 50.7 ± 11.0%), and by the genetic deletion of TRPA1 ((% inhibition: xylene 66.6 ± 16.7% and toluene 75 ± 0%). In addition, the topical application of xylene and toluene to the mouse paw elicited nociceptive responses, which were significantly reduced by oral treatment with HC-030031 ((% of inhibition: 84.9 ± 1.3% and 27.1 ± 8.0%, respectively); nociceptive responses were almost completely abolished in Trpa1−/−mice. Our data suggest that the activation of TRPA1 could be involved in some of the symptoms of irritant-mediated contact dermatitis, such as oedema, pain and neurogenic inflammation.