{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:16:36Z","timestamp":1760235396037,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C209052112-3"],"award-info":[{"award-number":["2019R1A2C209052112-3"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HR16C0002"],"award-info":[{"award-number":["HR16C0002"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The activation of signal transducer and activator of transcription 3 (STAT3), as well as up-regulation of cytokines and growth factors to promote STAT3 activation, have been found in the epidermis of psoriatic lesions. Recently, a series of synthetic compounds possessing the Michael acceptor have been reported as STAT3 inhibitors by covalently binding to cysteine of STAT3. We synthesized a Michael acceptor analog, SKSI-0412, and confirmed the binding affinity between STAT3 and SKSI-0412. We hypothesized that the SKSI-0412 can inhibit interleukin (IL)-17A-induced inflammation in keratinocytes. The introduction of IL-17A increased the phosphorylation of STAT3 in keratinocytes, whereas the inactivation of STAT3 by SKSI-0412 reduced IL-17A-induced STAT3 phosphorylation and I\u03baB\u03b6 expression. In addition, human \u03b2 defensin-2 and S100A7, which are regulated by I\u03baB\u03b6, were significantly decreased with SKSI-0412 administration. We also confirmed that SKSI-0412 regulates cell proliferation, which is the major phenotype of psoriasis. Based on these results, we suggest targeting STAT3 with SKSI-0412 as a novel therapeutic strategy to regulate IL-17A-induced psoriatic inflammation in keratinocytes.<\/jats:p>","DOI":"10.3390\/ijms22168813","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:27:45Z","timestamp":1629149265000},"page":"8813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Michael Acceptor Analogue, SKSI-0412, Down-Regulates Inflammation and Proliferation Factors through Suppressing Signal Transducer and Activator of Transcription 3 Signaling in IL-17A-Induced Human Keratinocyte"],"prefix":"10.3390","volume":"22","author":[{"given":"A-Ram","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Dermatology, School of Medicine, CHA University, 120 Haeryong-ro, Pocheon 11160, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-3723","authenticated-orcid":false,"given":"Seungbeom","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, CHA University, 120 Haeryong-ro, Pocheon 11160, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung U","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, CHA Bundang Mediacal Center, School of Medicine, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-7942","authenticated-orcid":false,"given":"Seung Hui","family":"Seok","sequence":"additional","affiliation":[{"name":"Department of Dermatology, CHA Bundang Mediacal Center, School of Medicine, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Ger","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, CHA University, 120 Haeryong-ro, Pocheon 11160, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-2400","authenticated-orcid":false,"given":"Dong Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, CHA Bundang Mediacal Center, School of Medicine, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0140-6736(03)12954-6","article-title":"Psoriasis","volume":"361","author":"Lebwohl","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri1689","article-title":"Getting under the skin: The immunogenetics of psoriasis","volume":"5","author":"Bowcock","year":"2005","journal-title":"Nat. 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