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In this study, we aimed to investigate the role of 17-AAG, a Hsp90 inhibitor, in inhibiting skin inflammation in AD and its effect on nuclear factor kappa-B (NF-\u03baB)\/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway. Topical application of 17-AAG was found to significantly improve inflammatory skin lesions, reduce epidermal thickness and mast cell infiltration, and decrease levels of proinflammatory cytokines in mice with AD-like skin lesions induced by using 2,4-dinitrochlorobenzene (1\u202f% and 0.5\u202f% DNCB). A reduced extent of p65 phosphorylation with declined protein expressions of NLRP3 and caspase-1 in the dorsal skin lesions of 17-AAG-treated AD mice compared to vehicle-treated AD mice. In HaCaT\u00a0cells inflamed by tumor necrosis factor \u03b1 (TNF-\u03b1)\/interferon \u03b3 (IFN-\u03b3), 17-AAG treatment significantly reduced the secretion of proinflammatory cytokines and chemokines, reduce the phosphorylation of p65, and decreased the protein expressions of NLRP3 and caspase-1. These results prove Hsp90 inhibitor 17-AAG could reduce skin inflammation and inhibit NF-\u03baB\/NLRP3 inflammasome activation in DNCB-induced mice and TNF-\u03b1\/IFN-\u03b3-induced human keratinocytes.<\/jats:p>","DOI":"10.1515\/biol-2025-1377","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:57:03Z","timestamp":1792252623000},"source":"Crossref","is-referenced-by-count":0,"title":["Hsp90 inhibitor 17-AAG reduces skin inflammation and inhibits NF-\u03baB\/NLRP3 inflammasome activation in DNCB-induced mice and TNF-\u03b1\/IFN-\u03b3-induced keratinocytes"],"prefix":"10.1515","volume":"21","author":[{"given":"Yuan-Yuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Dermatology, Cangnan People\u2019s Hospital , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Third People\u2019s Hospital of Cangnan County , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"2026101715565567898_j_biol-2025-1377_ref_001","doi-asserted-by":"crossref","unstructured":"Meledathu, S, Naidu, MP, Brunner, PM. 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