{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:02:42Z","timestamp":1790301762112,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"Abstract<\/jats:title>Irritant contact dermatitis (ICD<\/jats:styled-content>) is an inflammatory reaction caused by chemical toxicity on the skin. The P<\/jats:styled-content>2X<\/jats:styled-content>7 receptor (P<\/jats:styled-content>2X<\/jats:styled-content>7R<\/jats:styled-content>) is a key mediator of cytokine release, which recruits immune cells to sites of inflammation. We investigated the role of P<\/jats:styled-content>2X<\/jats:styled-content>7R<\/jats:styled-content> in croton oil (C<\/jats:styled-content>rO<\/jats:styled-content>)\u2010induced ICD<\/jats:styled-content> using in vitro<\/jats:italic> and in vivo<\/jats:italic> approaches. ICD<\/jats:styled-content> was induced in vivo<\/jats:italic> by C<\/jats:styled-content>rO<\/jats:styled-content> application on the mouse ear and in vitro<\/jats:italic> by incubation of murine macrophages and dendritic cells (DC<\/jats:styled-content>s) with C<\/jats:styled-content>rO<\/jats:styled-content> and ATP<\/jats:styled-content>. Infiltrating cells were identified by flow cytometry, histology and myeloperoxidase (MPO<\/jats:styled-content>) determination. Effects of the ATP<\/jats:styled-content> scavenger apyrase were assessed to investigate further the role of P<\/jats:styled-content>2X<\/jats:styled-content>7R<\/jats:styled-content> in ICD<\/jats:styled-content>. Animals were also treated with N<\/jats:styled-content>\u20101330, a caspase\u20101 inhibitor, or with clodronate, which induces macrophage apoptosis. C<\/jats:styled-content>rO<\/jats:styled-content> application induced severe inflammatory G<\/jats:styled-content>r1+<\/jats:sup> cell infiltration and increased MPO<\/jats:styled-content> levels in the mouse ear. Selective P<\/jats:styled-content>2X<\/jats:styled-content>7R<\/jats:styled-content> antagonism with A<\/jats:styled-content>438079 or genetic P<\/jats:styled-content>2X<\/jats:styled-content>7R<\/jats:styled-content> deletion reduced the neutrophil infiltration. Clodronate administration significantly reduced G<\/jats:styled-content>r1+<\/jats:sup> cell infiltration and local IL<\/jats:styled-content>\u20101\u03b2 levels. In vitro<\/jats:italic> experiments confirmed that A<\/jats:styled-content>438079 or apyrase treatment prevented the increase in IL<\/jats:styled-content>\u20101\u03b2 that was evoked by macrophage and DC<\/jats:styled-content> incubation with C<\/jats:styled-content>rO<\/jats:styled-content> and ATP<\/jats:styled-content>. These data support a key role for P<\/jats:styled-content>2X<\/jats:styled-content>7 in ICD<\/jats:styled-content>\u2010mediated inflammation via modulation of inflammatory cells. It is tempting to suggest that P<\/jats:styled-content>2X<\/jats:styled-content>7R<\/jats:styled-content> inhibition might be an alternative ICD<\/jats:styled-content> treatment.<\/jats:p>","DOI":"10.1111\/exd.12094","type":"journal-article","created":{"date-parts":[[2013,1,19]],"date-time":"2013-01-19T05:29:22Z","timestamp":1358573362000},"page":"184-188","source":"Crossref","is-referenced-by-count":26,"title":["P<\/scp>2X<\/scp>7 receptor is required for neutrophil accumulation in a mouse model of irritant contact dermatitis"],"prefix":"10.1111","volume":"22","author":[{"given":"Gabriela L.","family":"da Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia D. M.","family":"Sperotto","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago J.","family":"Borges","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Laborat\u00f3rio de Imunologia Celular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bonorino","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Laborat\u00f3rio de Imunologia Celular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina M.","family":"Takyia","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro \u2010 UFRJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson","family":"Coutinho\u2010Silva","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro \u2010 UFRJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Campos","sequence":"additional","affiliation":[{"name":"Faculdade de Odontologia Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Instituto de Toxicologia e Farmacologia Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael F.","family":"Zanin","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Laborat\u00f3rio de Imunologia Celular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Instituto de Toxicologia e Farmacologia Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda B.","family":"Morrone","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Faculdade de Farm\u00e1cia Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"},{"name":"Instituto de Toxicologia e Farmacologia Pontificia Universidade Cat\u00f3lica do Rio Grande do Sul \u2010PUCRS Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2622"},{"key":"e_1_2_9_3_1","first-page":"284","volume":"14","author":"Saint\u2010Mezard P","year":"2004","journal-title":"Eur J Dermatol"},{"key":"e_1_2_9_4_1","first-page":"394","volume":"71","author":"Nosbaum A","year":"2010","journal-title":"Arch Mal Prof Enviro"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000178869"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01982641"},{"key":"e_1_2_9_7_1","first-page":"65","volume":"9","author":"Krasteva 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