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Novel benzoxazole derivatives DCPAB and HPAB attenuate Th1 cell-mediated inflammation through T-bet suppression
- Title
- Novel benzoxazole derivatives DCPAB and HPAB attenuate Th1 cell-mediated inflammation through T-bet suppression
- Authors
- Oh Y.J.; Kim D.; Oh S.; Jang E.J.; Won H.Y.; Jeong H.; Jeong M.G.; Choo H.-Y.P.; Hwang E.S.
- Ewha Authors
- 박혜영; 황은숙; 정하나
- SCOPUS Author ID
- 박혜영; 황은숙; 정하나
- Issue Date
- 2017
- Journal Title
- Scientific Reports
- ISSN
- 2045-2322
- Citation
- Scientific Reports vol. 7
- Publisher
- Nature Publishing Group
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Interferon-γ (IFN-γ), a critical inflammatory cytokine, is primarily produced by T helper 1 (Th1) cells and accelerates the pathogenesis of inflammatory colitis. Pharmacological suppression of IFN-γ production attenuates dysregulated inflammatory responses and may be beneficial for treating inflammatory disease. In this study, we aimed to discover potent anti-inflammatory compounds that suppress IFN-γ production and found that the novel benzoxazole derivatives, 2-((3,4-dichlorophenyl) amino) benzo[d]xazol-5-ol (DCPAB) and 2-((3,4-hydroxyphenyl) amino) benzo[d]xazol-5-ol (HPAB), suppressed IFN-γ production by T cells. Treatment of CD4+ T cells with DCPAB and HPAB selectively inhibited Th1 cell development, and DCPAB more potently suppressed IFN-γ than HPAB did. Interestingly, DCPAB and HPAB significantly suppressed the expression of T-box containing protein expressed in T cells (T-bet) that activates IFN-γ gene transcription. DCPAB additionally suppressed transcriptional activity of T-bet on IFN-γ gene promoter, whereas HPAB had no effect on T-bet activity. IFN-γ suppressive activity of DCPAB and HPAB was impaired in the absence of T-bet but was retrieved by the restoration of T-bet in T-bet-deficient T cells. Furthermore, DCPAB and HPAB attenuated inflammatory colitis development that was induced by CD4+ T cells in vivo. We suggest that the novel benzoxazole derivatives, DCPAB and HPAB, may have therapeutic effects on inflammatory colitis. © The Author(s) 2017.
- DOI
- 10.1038/srep42144
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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