title: Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice.
abstract: 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-κB 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.
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Center for Neuro-Medicine, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ae Jin
authors.initials: AJ
authors.lastname: Jeong
authors.affiliation: Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dae-Jeon University, Daejeon, Republic of Korea.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Beauty Design, Halla Univesity, Wonju, Republic of Korea.
authors.forename: Sung-Ja
authors.initials: SJ
authors.lastname: Rhie
authors.affiliation: Department of Health & Beauty Science, GyeongBuk Provincial College, Yecheon, Republic of Korea.
authors.forename: Jung Sook
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Biotechnology, Research Institute of Inflammatory Diseases, College of Biomedical and Health Science, Konkuk University, Chungju, Republic of Korea.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Comparative Biomedicine Research Branch, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Yong-Nyun
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea; Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Center for Neuro-Medicine, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea; Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Science Project (BK21(PLUS)), Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: sangkyu@snu.ac.kr.
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Science Project (BK21(PLUS)), Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: protein0826@snu.ac.kr.
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D056747:Immunomodulation / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012680:Sensitivity and Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C561472:2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo(1,3)oxathiol-4-one; D019086:Bridged Bicyclo Compounds, Heterocyclic