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Vitamin D3 (VD3) has excellent anti\u2010inflammatory properties and is considered as a potential candidate for the treatment of NM\u2010induced dermal toxicity; however, the underlying mechanisms are currently unclear. Cyclooxygenase\u20102 (COX2; a widely used marker of skin inflammation) plays a key role in NM\u2010induced cutaneous inflammation. Herein, we initially confirmed that NM markedly promoted COX2 expression in vitro and in vivo. NM also increased NOD\u2010like receptor family pyrin domain containing 3 (NLRP3) expression, caspase\u20101 activity, and interleukin\u20101\u03b2 (IL\u20101\u03b2) release. Notably, treatment with a caspase\u20101 inhibitor (zYVAD\u2010fmk), NLRP3 inhibitor (MCC950), and\n                    <jats:italic>NLRP3<\/jats:italic>\n                    or\n                    <jats:italic>caspase\u20101<\/jats:italic>\n                    siRNA attenuated NM\u2010induced NLRP3 inflammasome activation, with subsequent suppression of COX2 expression and IL\u20101\u03b2 release in keratinocytes. Meanwhile, NM increased mitochondrial reactive oxygen species (mtROS) and decreased manganese superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) activities. Mito\u2010TEMPO (a mtROS scavenger) ameliorated NM\u2010caused NLRP3 inflammasome activation in keratinocytes. Moreover, VD3 improved SIRT3 and SOD2 activities, decreased mtROS contents, inactivated the NLRP3 inflammasome, and attenuated cutaneous inflammation induced by NM in vitro and in vivo. The beneficial activity of VD3 against NM\u2010triggered cutaneous inflammation was enhanced by the inhibitors of IL\u20101, mtROS, NLRP3, caspase\u20101, and\n                    <jats:italic>NLRP3<\/jats:italic>\n                    or\n                    <jats:italic>caspase\u20101<\/jats:italic>\n                    siRNAs, which was abolished in SIRT3 inhibitor or\n                    <jats:italic>SIRT3<\/jats:italic>\n                    siRNA\u2010treated keratinocytes and skins from SIRT3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In conclusion, VD3 ameliorated NM\u2010induced cutaneous inflammation by inactivating the NLRP3 inflammasome, which was partially mediated through the SIRT3\u2013SOD2\u2013mtROS signaling pathway.\n                  <\/jats:p>","DOI":"10.1002\/ctm2.312","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T12:58:24Z","timestamp":1613307504000},"source":"Crossref","is-referenced-by-count":59,"title":["Vitamin D3 ameliorates nitrogen mustard\u2010induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3\u2013SOD2\u2013mtROS signaling pathway"],"prefix":"10.1002","volume":"11","author":[{"given":"Xunhu","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Chemical Defense Medicine, School of Military Preventive Medicine Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Institute of Toxicology, School of Military Preventive Medicine Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Xinqiao Hospital Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Chemical Defense Medicine, School of Military Preventive Medicine Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Institute of Toxicology, School of Military Preventive Medicine Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanpeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Chemical Defense Medicine, School of Military Preventive Medicine Third Military Medical University (Army 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