I-BET151 selectively regulates IL-6 production.
I-BET151 selectively regulates IL-6 production.
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DOI：
10.1016/j.bbadis.2014.05.013
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发表时间：
2014-09
影响因子：
6.2
通讯作者：
Beurel, Eleonore
中科院分区：
文献类型：
--
作者：
Barrett, Elyse;Brothers, Shaun;Wahlestedt, Claes;Beurel, Eleonore
炎症反应的抑制对于清除病原体至关重要。虽然多种炎性细胞因子的产生被认为是由共同的机制调节，但最近的证据表明，某些细胞因子的表达受到表观遗传调节机制的差异调节。在这项研究中，我们发现，在脂多糖（LPS）刺激的RAW 264.7细胞中，BET布罗莫结构域蛋白（BRD）抑制剂I-BET 151选择性抑制IL-6的产生，而在所用IBET 151浓度下，I-BET 151并不改变其他几种细胞因子（TNFα、IL-1β和IL-10）的产生。I-BET 151可抑制CBP与IL-6启动子的结合，但不影响p65-NF-κB的乙酰化、磷酸化、核转位和DNA结合。在体内，在多发性硬化的实验性自身免疫性脑脊髓炎小鼠模型中的I-BET 151治疗减少了早期临床症状，这被认为依赖于细胞因子的产生。总之，这些数据表明，靶向表观遗传相关蛋白，如BET蛋白，可以提供一种减少炎症和炎性疾病，如多发性硬化症的严重程度的策略。
Orchestration of the inflammatory response is crucial for clearing pathogens. Although the production of multiple inflammatory cytokines has been thought to be regulated by common mechanisms, recent evidence indicates that the expression of some cytokines is differentially regulated by epigenetic regulatory mechanisms. In this study, we found that IL-6 production is selectively inhibited by the BET bromodomain protein (BRD) inhibitor I-BET151 in RAW264.7 cells stimulated with lipopolysaccharide (LPS), whereas I-BET151 did not alter the production of several other cytokines (TNFα, IL-1β and IL-10) at the concentration of IBET151 used. I-BET151 prevented the binding of CBP to the promoter of IL-6, but I-BET151 did not affect acetylation, phosphorylation, nuclear translocation, or DNA binding of p65-NF-κB. In vivo, I-BET151 treatment in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis decreased the early clinical symptoms, which are thought to be dependent on cytokine production. Altogether, these data suggest that targeting epigenetic-related proteins, such as BET proteins, may provide a strategy to reduce inflammation and the severity of inflammatory diseases, such as multiple sclerosis.
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影响因子：
30.5
作者：
通讯作者：
--
选择性抑制BET溴结构域。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16
作者：
Yang, ZY;Yik, JHN;Zhou, Q
通讯作者：
Zhou, Q
影响因子：
64.5
作者：
Delmore JE;Issa GC;Lemieux ME;Rahl PB;Shi J;Jacobs HM;Kastritis E;Gilpatrick T;Paranal RM;Qi J;Chesi M;Schinzel AC;McKeown MR;Heffernan TP;Vakoc CR;Bergsagel PL;Ghobrial IM;Richardson PG;Young RA;Hahn WC;Anderson KC;Kung AL;Bradner JE;Mitsiades CS
通讯作者：
Mitsiades CS
影响因子：
11.4
作者：
Ishinaga, Hajime;Jono, Hirofumi;Li, Jian-Dong
通讯作者：
Li, Jian-Dong