{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:26:54Z","timestamp":1792114014932,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006706","name":"Tampereen Tuberkuloosis\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010600","name":"Tays","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010600","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methylisothiazolinone (MIT) is a known inducer of allergic contact dermatitis that is used as a preservative and a biocide in consumer products. Transient receptor potential ankyrin 1 (TRPA1) is a non\u2010selective cation channel expressed in neurons and in some nonneuronal cells including keratinocytes. In neurons, TRPA1 mediates itch, pain and neurogenic inflammation. It has also been shown that TRPA1\u2010deficient animals have reduced expression of inflammatory cytokines in experimental models of allergic contact dermatitis. Therefore, we aimed to test the hypothesis that TRPA1 is activated by MIT and mediates MIT\u2010induced inflammatory conditions. In Fluo 3\u2010AM intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    measurements MIT caused a dose\u2010dependent increase in the intracellular calcium which was inhibited with the TRPA1\u2010antagonist A\u2010967079. In whole\u2010cell patch clamp recordings, MIT was confirmed to induce currents blocked by A\u2010967079. EC\n                    <jats:sub>50<\/jats:sub>\n                    values were 2.17\u2009\u03bcM at +70\u2009mV and 6.28\u2009\u03bcM at \u221270\u2009mV in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010free conditions. Mutation of the cysteine 621 in TRPA1 lowered the potency of MIT to activate the channel. In the mouse model of MIT\u2010induced acute inflammatory paw edema, mice treated with a TRPA1 antagonist as well as TRPA1\u2010deficient mice had reduced edema formation. In addition, TRPA1\u2010deficient mice sensitized to MIT had reduced elevation of IL\u20104 expression in skin following exposure to MIT when compared to wild\u2010type mice. In conclusion, we report here, for the first time, that the preservative and known contact sensitizer MIT is a potent agonist of TRPA1 and that TRPA1 mediates some of the effects of MIT in inflammatory conditions. These results together with the previous findings suggest that TRPA1 is a factor in the pathogenesis of type 2\u2009T\u2010helper cell (Th2)\u2010skewed contact allergy and as such a potential drug target to treat Th2\u2010driven diseases.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70053","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T02:26:05Z","timestamp":1746584765000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Contact Allergen Methylisothiazolinone (\n                    <scp>MIT<\/scp>\n                    ) is a Potent Activator of the\n                    <scp>TRPA1<\/scp>\n                    Ion Channel"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-040X","authenticated-orcid":false,"given":"Ilari","family":"M\u00e4ki\u2010Opas","sequence":"first","affiliation":[{"name":"The Immunopharmacology Research 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