Lee, Hyun Gyu Cho, Nam-chul Jeong, Ae Jin Li, Yu-Chen Rhie, Sung-Ja Choi, Jung Sook Lee, Kwang-Ho Kim, Youngsoo Kim, Yong-Nyun Kim, Myoung-Hwan Pae, Ae Nim Ye, Sang-Kyu Kim, Byung-Hak 2024-01-20T05:04:39Z 2024-01-20T05:04:39Z 2021-09-03 2016-01 0022-202X https://pubs.kist.re.kr/handle/201004/124574 T-cell-mediated immune responses play an important role in body protection. However, aberrantly activated immune responses are responsible for inflammatory and autoimmune diseases. The regulation of pathologic immune responses may be a potential therapeutic strategy for the treatment of these diseases. Despite that multiple pharmacologic properties of benzoxathiole derivatives have been defined, the molecular mechanisms underlying these properties remain to be clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune responses and ameliorated experimentally induced inflammatory skin diseases both in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4(+) T-cell subsets by regulating the expression and production of T-cell lineage-specific master transcription factors and cytokines and activating the signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited TCR-mediated Akt and NF-kappa B signaling. Topical application of BOT-4-one ameliorated experimentally induced inflammatory skin diseases in mice models such as 2,4,6-trinitrochlorobenzene-induced contact and atopic dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing the pathogenic CD4(+) T cell differentiation and overall immune responses. English ELSEVIER SCIENCE INC KAPPA-B-KINASE REGULATORY T-CELLS SRC-FAMILY KINASES IMMUNE-RESPONSES DIFFERENTIATION ACTIVATION SURVIVAL DISEASE BETA MACROPHAGES Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice Article 10.1038/JID.2015.384 1 JOURNAL OF INVESTIGATIVE DERMATOLOGY, v.136, no.1, pp.107 - 116 JOURNAL OF INVESTIGATIVE DERMATOLOGY 136 1 107 116 scie scopus 000377952900021 2-s2.0-84959552810 Dermatology Dermatology Article KAPPA-B-KINASE REGULATORY T-CELLS SRC-FAMILY KINASES IMMUNE-RESPONSES DIFFERENTIATION ACTIVATION SURVIVAL DISEASE BETA MACROPHAGES Immunomodulatory Benzoxathiole BOT-4-One