{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:36:17Z","timestamp":1785832577890,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000296","name":"British Skin Foundation","doi-asserted-by":"publisher","award":["032_BSFSG_19"],"award-info":[{"award-number":["032_BSFSG_19"]}],"id":[{"id":"10.13039\/501100000296","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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Decreased epidermal high\u2010mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis (SJS\/TEN). Etanercept, an anti\u2010tumor necrosis factor therapeutic, is effective in the treatment of SJS\/TEN. The objective was to characterize antitumor necrosis factor\u2010alpha (TNF\u2010\u03b1)\u2010mediated HMGB1 keratinocyte\/epidermal release and etanercept modulation. HMGB1 release from TNF\u2010\u03b1 treated (\u00b1\u2009etanercept), or doxycycline\u2010inducible RIPK3 or Bak\u2010expressing human keratinocyte cells (HaCaTs) was determined by western blot\/ELISA. Healthy skin explants were treated with TNF\u2010\u03b1 or serum (1:10 dilution) from immune checkpoint inhibitor\u2010tolerant, lichenoid dermatitis or SJS\/TEN patients\u2009\u00b1\u2009etanercept. Histological and immunohistochemical analysis of HMGB1 was undertaken. TNF\u2010\u03b1 induced HMGB1 release in vitro via both necroptosis and apoptosis. Exposure of skin explants to TNF\u2010\u03b1 or SJS\/TEN serum resulted in significant epidermal toxicity\/detachment with substantial HMGB1 release which was attenuated by etanercept. Whole\u2010slide image analysis of biopsies demonstrated significantly lower epidermal HMGB1 in pre\u2010blistered SJS\/TEN versus control (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Keratinocyte HMGB1 release, predominantly caused by necroptosis, can be attenuated by etanercept. Although TNF\u2010\u03b1 is a key mediator of epidermal HMGB1 release, other cytokines\/cytotoxic proteins also contribute. Skin explant models represent a potential model of SJS\/TEN that could be utilized for further mechanistic studies and targeted therapy screening.<\/jats:p>","DOI":"10.1111\/1346-8138.16847","type":"journal-article","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T05:30:53Z","timestamp":1685770253000},"page":"1129-1139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>TNF<\/scp>\u2010\u03b1 induced extracellular release of keratinocyte high\u2010mobility group box 1 in <scp>Stevens\u2010Johnson<\/scp> syndrome\/toxic epidermal necrolysis: Biomarker and putative mechanism of pathogenesis"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1276-3879","authenticated-orcid":false,"given":"Gospel","family":"Nwikue","sequence":"first","affiliation":[{"name":"Department Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology University of 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