{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:30:42Z","timestamp":1760059842938,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Government (MIST)","award":["2022R1A2C1004096","2021R1A5A2021614","HI22C1988","RS-2025-16063085","RS-2025-25410994"],"award-info":[{"award-number":["2022R1A2C1004096","2021R1A5A2021614","HI22C1988","RS-2025-16063085","RS-2025-25410994"]}]},{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["2022R1A2C1004096","2021R1A5A2021614","HI22C1988","RS-2025-16063085","RS-2025-25410994"],"award-info":[{"award-number":["2022R1A2C1004096","2021R1A5A2021614","HI22C1988","RS-2025-16063085","RS-2025-25410994"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Estrogen-related receptor \u03b3 (ERR\u03b3) has been reported to regulate various inflammation-related diseases. Herein, we attempted to evaluate the effects of DN200434 as a modulator for ERR\u03b3 in mice with atopic dermatitis (AD). Levels of mRNA and protein expression for ERR\u03b3 were evaluated in normal and DNCB-induced AD-diagnosed skin. The effects of DN200434 on the chemokines, inflammatory cytokines, and AKT\/MAPK\/NF\u03baB pathway signaling were investigated in TNF-\u03b1\/IFN-\u03b3-treated HaCaT cells. DNCB-induced AD mice received DN200434 intraperitoneally for 10 days. Epidermal thickness at the dorsal aspect of the inflamed skin, spleen index, serum IgE levels, and proinflammatory cytokine levels in the skin lesions were measured. Histopathological evaluations, including assessments of epidermal hyperplasia, dermal inflammation, hyperkeratosis, folliculitis, and mast cell counts, were performed to confirm diagnostic features. Significant elevations in ERR\u03b3 expression at the RNA and protein levels were observed in DNCB-induced AD lesions. DN200434 suppressed chemokine and inflammatory cytokine expression and inhibited the elevated phosphorylation levels of AKT, ERK, p38, and NF\u03baB in TNF-\u03b1\/IFN-\u03b3-treated HaCaT cells. Treatment with DN200434 alleviated DNCB-induced AD symptoms. The histopathological score and levels of infiltrated mast cells were also markedly lower in DN200434-treated AD mice than in vehicle-treated AD mice. Consistently, DN200434 reduced the serum IgE level and mRNA expression of TNF\u03b1 and IL-6 in AD-diagnosed lesions. Collectively, our findings indicated the feasibility of ERR\u03b3 as a therapeutic target for the regulation of AD and that DN200434 can be a useful therapeutic agent in treating AD.<\/jats:p>","DOI":"10.3390\/ijms26146959","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:33:53Z","timestamp":1753090433000},"page":"6959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Therapeutic Potential of Estrogen-Related Receptor \u03b3 Inverse Agonists in Atopic Dermatitis-like Lesions"],"prefix":"10.3390","volume":"26","author":[{"given":"Ju Hyeon","family":"Bae","sequence":"first","affiliation":[{"name":"Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), 80 Cheombok-ro Dong-gu, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), 80 Cheombok-ro Dong-gu, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Eon","family":"Lee","sequence":"additional","affiliation":[{"name":"Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), 80 Cheombok-ro Dong-gu, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Kyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), 80 Cheombok-ro Dong-gu, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-968X","authenticated-orcid":false,"given":"Jae-Han","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, 807 Hoguk-ro, Buk-gu, Daegu 41404, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Hyun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), 80 Cheombok-ro Dong-gu, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1600-065X.2011.01027.x","article-title":"Atopic dermatitis: A disease of altered skin barrier and immune dysregulation","volume":"242","author":"Boguniewicz","year":"2011","journal-title":"Immunol. 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