{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:32:12Z","timestamp":1780061532203,"version":"3.54.0"},"reference-count":8,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T00:00:00Z","timestamp":1427241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG KA 3438\/1-1"],"award-info":[{"award-number":["DFG KA 3438\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 306\/2"],"award-info":[{"award-number":["EXC 306\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>A broad range of immunosuppressive and immunomodulatory effects of heat shock protein 90 (Hsp90) blockade has been described in models of autoimmune bullous diseases, but the direct contribution of this chaperone to neutrophil effector pathways in the context of autoantibody\u2010driven blistering is generally unknown. Therefore, this has been addressed in the current study on the basis of the subepidermal blistering disease epidermolysis bullosa acquisita (EBA) characterized by autoantibodies against type VII collagen, in which a crucial role of neutrophils and both their reactive oxygen species and matrix metalloproteinases in mediating tissue injury has been established. First, the Hsp90 antagonist 17\u2010DMAG dose\u2010dependently inhibited dermal\u2010epidermal separation ex vivo in cryosections of human skin induced by co\u2010incubation of EBA patient autoantibodies with neutrophils from healthy blood donors. Next, 17\u2010DMAG dose\u2010dependently suppressed production and release of reactive oxygen species by human neutrophils induced by both fMLP\u00a0\u00b1\u00a0LPS and EBA\u2010specific immune complexes. In addition, co\u2010immunoprecipitation studies revealed that extracellular Hsp90 interacted with secreted matrix metalloproteinases 2 and 12 in sera of EBA patients, suggesting that these basement membrane\u2010degrading proteolytic enzymes are client proteins of Hsp90 and dependent on its chaperone function. Our findings add to the knowledge of the multimodal anti\u2010inflammatory effects of Hsp90 blockade and implicate that Hsp90 is closely involved in the effector mechanisms of neutrophil\u2010driven autoantibody\u2010induced tissue damage, thus being a relevant therapeutic target in patients with neutrophil\u2010mediated autoimmune diseases such as inflammatory types of EBA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/exd.12680","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T06:53:11Z","timestamp":1425538391000},"page":"471-473","source":"Crossref","is-referenced-by-count":25,"title":["Heat shock protein 90 is required for <i>ex vivo<\/i> neutrophil\u2010driven autoantibody\u2010induced tissue damage in experimental epidermolysis bullosa acquisita"],"prefix":"10.1111","volume":"24","author":[{"given":"Stefan","family":"Tukaj","sequence":"first","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Hellberg","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ueck","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"H\u00e4nsel","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unni","family":"Samavedam","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Zillikens","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Laskay","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kasperkiewicz","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,25]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-314609"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12476"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-014-0513-8"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2157"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1674"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64182-X"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1131"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70169-4"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.12680","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.12680","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:41:22Z","timestamp":1695573682000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.12680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,25]]},"references-count":8,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/exd.12680"],"URL":"https:\/\/doi.org\/10.1111\/exd.12680","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,25]]}}}