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http://dx.doi.org/10.5483/BMBRep.2017.50.12.194

JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF-κB axis  

Lee, Min Bum (School of Medicine, Konkuk University)
Lee, Jun-Ho (Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University)
Hong, Seong Hwi (School of Medicine, Konkuk University)
You, Jueng Soo (School of Medicine, Konkuk University)
Nam, Seung Taek (School of Medicine, Konkuk University)
Kim, Hyun Woo (School of Medicine, Konkuk University)
Park, Young Hwan (School of Medicine, Konkuk University)
Lee, Dajeong (School of Medicine, Konkuk University)
Min, Keun Young (School of Medicine, Konkuk University)
Park, Yeong-Min (School of Medicine, Konkuk University)
Kim, Young Mi (College of Pharmacy, Duksung Women's University)
Kim, Hyuk Soon (School of Medicine, Konkuk University)
Choi, Wahn Soo (School of Medicine, Konkuk University)
Publication Information
BMB Reports / v.50, no.12, 2017 , pp. 640-646 More about this Journal
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 $NF-{\kappa}B$ on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with $NF-{\kappa}B$ 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.
Keywords
BRD4; IL-10; JQ1; $NF-{\kappa}B$; Regulatory B cells;
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