{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:03:34Z","timestamp":1789898614252,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K15517"],"award-info":[{"award-number":["17K15517"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies have shown that sparse distribution of regulatory T cells (Tregs) in the skin might be involved in the onset of severe cutaneous adverse drug reactions such as Stevens\u2013Johnson syndrome and toxic epidermal necrolysis. Treg migration toward epithelial cells is regulated by certain chemokines, including TARC\/CCL17 and MDC\/CCL22. In this study, we analyzed the effect of allopurinol (APN), a drug known to cause severe adverse reactions, on the expression of factors affecting Treg migration and the mechanisms involved. APN inhibited the tumor necrosis factor (TNF)\u2010\u03b1\u2010 and interferon (IFN)\u2010\u03b3\u2010associated expression of <jats:italic>TARC<\/jats:italic>\/<jats:italic>CCL17<\/jats:italic> and <jats:italic>MDC<\/jats:italic>\/<jats:italic>CCL22<\/jats:italic> mRNA in HaCaT cells in a dose\u2010dependent manner. Consistent with this, APN also suppressed TNF\u2010\u03b1\u2010 and IFN\u2010\u03b3\u2010induced production of TARC\/CCL17 and MDC\/CCL22 proteins and the migration of C\u2010C chemokine receptor type 4\u2010positive cells. Activity of the transcription factors NF\u2010\u03baB and STAT1, which are involved in TARC\/CCL17 and MDC\/CCL22 expression, was also investigated. APN inhibited activation of NF\u2010\u03baB, but not that of STAT1. Furthermore, it restricted p38 MAPK phosphorylation. These results suggest that APN inhibits TNF\u2010\u03b1\u2010 and IFN\u2010\u03b3\u2010induced TARC\/CCL17 and MDC\/CCL22 production through downregulation of p38 MAPK and NF\u2010\u03baB signaling, resulting in the sparse distribution of Tregs in the skin of patients with APN\u2010associated Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis.<\/jats:p>","DOI":"10.1002\/jat.3522","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T05:27:01Z","timestamp":1506403621000},"page":"274-283","source":"Crossref","is-referenced-by-count":17,"title":["Allopurinol suppresses expression of the regulatory T\u2010cell migration factors TARC\/CCL17 and MDC\/CCL22 in HaCaT keratinocytes via restriction of nuclear factor\u2010\u03baB activation"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7660-2065","authenticated-orcid":false,"given":"Makoto","family":"Osabe","sequence":"first","affiliation":[{"name":"Regulatory 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