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

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 cont...

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Published inBMB reports Vol. 50; no. 12; pp. 640 - 646
Main Authors Lee, Min Bum, Lee, Jun-Ho, Hong, Seong Hwi, You, Jueng Soo, Nam, Seung Taek, Kim, Hyun Woo, Park, Young Hwan, Lee, Dajeong, Min, Keun Young, Park, Yeong-Min, Kim, Young Mi, Kim, Hyuk Soon, Choi, Wahn Soo
Format Journal Article
LanguageEnglish
Published Korea (South) Korean Society for Biochemistry and Molecular Biology 01.12.2017
생화학분자생물학회
Subjects
Animals
Azepines - chemistry
Azepines - pharmacology
B-Lymphocytes, Regulatory - drug effects
B-Lymphocytes, Regulatory - metabolism
Dose-Response Relationship, Drug
Interleukin-10 - biosynthesis
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred C57BL
NF-kappa B - metabolism
Nuclear Proteins - metabolism
Toll-Like Receptor 4 - metabolism
Transcription Factors - metabolism
Triazoles - chemistry
Triazoles - pharmacology
화학
Online AccessGet full text
ISSN1976-6696
1976-670X
DOI10.5483/BMBRep.2017.50.12.194

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Summary: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 bromodomaincontaining 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. [BMB Reports 2017; 50(12): 640-646].
Bibliography:These authors contributed equally to this work.
ISSN:1976-6696
1976-670X
DOI:10.5483/BMBRep.2017.50.12.194