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

BMB Reports

Seong Hwi Hong^1¹  Jun-Ho Lee^2²  Min Bum Lee^1³ 

[1] College of Pharmacy, Duksung Womens University, Seoul 01369, Korea^3;Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Korea^2;School of Medicine, Konkuk University, Chungju 27478, Korea^1

关键词: BRD4;   

DOI  :  10.5483/BMBRep.2017.50.12.194

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

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.

【 授权许可】

Unknown