{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:08:31Z","timestamp":1791083311879,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science &amp; ICT","award":["2019M3A9I3091696"],"award-info":[{"award-number":["2019M3A9I3091696"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-\u03b1\/IFN-\u03b3-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-\u03b1\/IFN-\u03b3 in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-\u03b1\/IFN-\u03b3-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-\u03baB, and p38 MAPK mediate TNF-\u03b1\/IFN-\u03b3-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-\u03b1\/IFN-\u03b3-induced phosphorylation of STAT1, NF-\u03baB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-\u03b1\/IFN-\u03b3-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-\u03baB, and p38 MAPK signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms22126428","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T10:27:07Z","timestamp":1623839227000},"page":"6428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Skullcapflavone II Suppresses TNF-\u03b1\/IFN-\u03b3-Induced TARC, MDC, and CTSS Production in HaCaT Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-5411","authenticated-orcid":false,"given":"Hanon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea"},{"name":"Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea"},{"name":"Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2925-3074","authenticated-orcid":false,"given":"Dong Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea"},{"name":"Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-5209","authenticated-orcid":false,"given":"Jang-Hee","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea"},{"name":"Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea"},{"name":"Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea"},{"name":"Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0140-6736(20)31286-1","article-title":"Atopic dermatitis","volume":"396","author":"Langan","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/1346-8138.15664","article-title":"Basics and recent advances in the pathophysiology of atopic dermatitis","volume":"48","author":"Nakahara","year":"2021","journal-title":"J. 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