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KMID : 0624620170500120640
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BMB Reports
2017 Volume.50 No. 12 p.640 ~ p.646
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JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF-κB axis
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Lee Min-Bum
Lee Jun-Ho
Hong Seong-Hwi
You Jueng-Soo
Nam Seung-Taek
Kim Hyun-Woo
Park Young-Hwan
Lee Da-Jeong
Min Keun-Young
Park Yeong-Min
Kim Young-Mi
Kim Hyuk-Soon
Choi Wahn-Soo
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Abstract
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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-κB on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with NF-κB 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.
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KEYWORD
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BRD4, IL-10, JQ1, NF-κB, Regulatory B cells
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