{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:12:54Z","timestamp":1791443574114,"version":"4.3.3"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T00:00:00Z","timestamp":1408665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2014,10]]},"abstract":"Abstract<\/jats:title>2,4\u2010Dinitrochlorobenzene (DNCB<\/jats:styled-content>) is widely used in human clinical studies and in experimental animal studies to evoke allergic contact dermatitis. 2,4\u2010Dinitrochlorobenzene is a potent immunogen capable of inducing contact sensitization in all humans exposed. However, the mechanism by which DNCB<\/jats:styled-content> evokes such symptoms is presently unknown. TRPA<\/jats:styled-content>1 is a nonselective cation channel that is expressed in peptidergic sensory neurons and fibroblasts. TRPA<\/jats:styled-content>1 activation was recently implicated in the pathophysiology of atopic dermatitis especially in transducing cutaneous itch signals. Here, we test the hypothesis that DNCB<\/jats:styled-content> acts as a TRPA<\/jats:styled-content>1 agonist and thereby evokes allergic symptoms. We found that DNCB<\/jats:styled-content> activates human TRPA<\/jats:styled-content>1 dose dependently in FLIPR<\/jats:styled-content> experiments with an EC<\/jats:styled-content>50<\/jats:sub> of 167\u00a0nM, an effect that was fully blocked by selective TRPA<\/jats:styled-content>1 antagonists C<\/jats:styled-content>hembridge\u20105861528 and A\u2010967079. Similarly, DNCB<\/jats:styled-content> activated nonselective TRPA<\/jats:styled-content>1 current in patch clamp studies. Neutralization of 3 critical cysteines in TRPA1 resulted in a loss of DNCB<\/jats:styled-content> agonism.<\/jats:p>","DOI":"10.1111\/all.12488","type":"journal-article","created":{"date-parts":[[2014,7,19]],"date-time":"2014-07-19T07:44:50Z","timestamp":1405755890000},"page":"1424-1427","source":"Crossref","is-referenced-by-count":28,"title":["Contact sensitizer 2,4\u2010dinitrochlorobenzene is a highly potent human TRPA<\/scp>1 agonist"],"prefix":"10.1111","volume":"69","author":[{"given":"M.","family":"Saarnilehto","sequence":"first","affiliation":[{"name":"In Vitro Biology R&D Orion Pharma Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Chapman","sequence":"additional","affiliation":[{"name":"In Vitro Biology R&D Orion Pharma Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Savinko","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Lindstedt","sequence":"additional","affiliation":[{"name":"Biomarkers R&D Orion Pharma Espoo Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. I.","family":"Lauerma","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Koivisto","sequence":"additional","affiliation":[{"name":"In Vitro Biology R&D Orion Pharma Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.66.3.337"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91757-Y"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.148"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00158-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.58"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1158-z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12138"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.057"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-229948"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300300"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.048"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2011.10.006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609598103"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.18.10835"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01786.x"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fall.12488","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.12488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T01:00:59Z","timestamp":1696467659000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.12488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,22]]},"references-count":15,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1111\/all.12488"],"URL":"https:\/\/doi.org\/10.1111\/all.12488","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,22]]}}}