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JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF-リB axis.
Hyuk Soon Kim1,*, Min Bum Lee1,#, JunHo Lee2,#, Seong Hwi Hong1, Jueng Soo You1, Seung Taek Nam1, Hyun Woo Kim1, Young Hwan Park1, Dajeong Lee1, Keun Young Min1, Yeong-Min Park1, Young Mi Kim3, Wahn Soo Choi1
1School of Medicine and 2Department of Biomedical Chemistry, College of Biomedical & Health science, Konkuk University,
3College of Pharmacy, Duksung Women's University
Abstract
Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells. While bromodomain-containing protein 4 (BRD4) was associated with NF-リB on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with NF-リB on IL-10 promoter. In summary, BRD4 is essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting JQ1 could be a potential candidate in regulating IL-10-producing regulatory B cells in cancer.
Abstract, Accepted Manuscript(in press) [Submitted on October 13, 2017, Accepted on November 28, 2017]
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