{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T16:40:54Z","timestamp":1785688854622,"version":"3.56.0"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009158","name":"Kawasaki Medical School","doi-asserted-by":"publisher","award":["R01B\u2010058"],"award-info":[{"award-number":["R01B\u2010058"]}],"id":[{"id":"10.13039\/501100009158","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009158","name":"Kawasaki Medical School","doi-asserted-by":"publisher","award":["R02B\u2010052"],"award-info":[{"award-number":["R02B\u2010052"]}],"id":[{"id":"10.13039\/501100009158","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Darier\u2019s disease (DD) and Hailey\u2013Hailey disease (HHD), belonging to a hereditary acantholytic dermatosis caused by mutations in <jats:italic>ATP2A2<\/jats:italic> and <jats:italic>ATP2C1<\/jats:italic>, respectively, are easily affected by eczema herpeticum (EH) induced by mostly herpes simplex virus (HSV) superinfection. However, the mechanisms by which those patients with DD or HHD are susceptible to HSV are not well elucidated. Here, we experienced two cases with DD, including three episodes of the exacerbation of DD after the development of severe EH. We serially measured serum cytokines before and after the development of EH and DD in these patients. Furthermore, we analyzed the effect of pro\u2010inflammatory cytokines on the mRNA expression of <jats:italic>ATP2A2<\/jats:italic> and <jats:italic>ATP2C1<\/jats:italic>, and HSV growth. The timing of EH onset in these patients was coincident with the increase in serum interleukin (IL)\u20106 and tumor necrosis factor (TNF)\u2010\u03b1 levels. Moreover, the exacerbation of DD occurred in the non\u2010lesional skin of EH after EH remission (mean 24\u00a0days, ranging 15\u201330\u00a0days after EH onset). IL\u20106 and TNF\u2010\u03b1 enhanced HSV\u20101 growth, and <jats:italic>ATP2A2<\/jats:italic> and <jats:italic>ATP2C1<\/jats:italic> mRNA levels were downregulated by IL\u20106 stimulation in cultured differentiated keratinocytes. Increased pro\u2010inflammatory cytokines IL\u20106 and TNF\u2010\u03b1 lead to development of severe EH lesions via accentuation of HSV growth. IL\u20106 acts as an exacerbating factor of DD and HHD by downregulating the expression of responsible genes.<\/jats:p>","DOI":"10.1111\/1346-8138.16097","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T07:33:38Z","timestamp":1628235218000},"page":"1607-1611","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Role of pro\u2010inflammatory cytokines in the pathophysiology of herpes simplex virus superinfection in Darier\u2019s disease"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-7033","authenticated-orcid":false,"given":"Takenobu","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Dermatology Kawasaki Medical School Kurashiki Japan"},{"name":"Department of Dermatology Kawasaki Medical School General Medical Center Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3701-5575","authenticated-orcid":false,"given":"Yumi","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kawasaki Medical School Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.13230"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.12.006"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781444317633.ch33"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.08.002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.11.027"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.02.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.05.019"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2018.09.006"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.06394.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/422325"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200002000-00042"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.150"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/907802"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.290"},{"key":"e_1_2_6_16_1","first-page":"1247","article-title":"Mortality in tocilizumab\u2010treated patients with COVID\u201019: a systematic review and meta\u2010analysis","volume":"38","author":"Berardicurti O","year":"2020","journal-title":"Clin Exp Rheumatol"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1346-8138.16097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T10:29:36Z","timestamp":1693218576000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.16097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":15,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/1346-8138.16097"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.16097","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,6]]},"assertion":[{"value":"2021-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}