The suppression of bromodomain and extra‐terminal domain inhibits vascular inflammation by blocking NF‐κB and MAPK activation

• DOI: 10.1111/bph.13657
• Publication Date: 2016-10-24T06:06:39Z
• Authors: Mingcheng Huang; Shan Zeng; Yaoyao Zou; Maohua Shi; Qian Qiu; Youjun Xiao; Guoqiang Chen; Xiuyan Yang; Liuqin Liang; Hanshi Xu
• Keywords: Blocking (statistics)

There is increasing evidence indicating that bromodomain and extra-terminal domain (BET) proteins play a critical role in the regulation of immune inflammatory responses; however, their contribution to vascular inflammation has not yet been elucidated. In this study, we investigated effect inhibiting BET on underlying mechanisms.HUVECs were isolated from fresh umbilical cords. JQ1, specific inhibitor, Brd shRNA used evaluate inflammation. Leukocyte adhesion HUVECs was measure by an assay. Western blot or immunohistochemical analysis detect protein expression. Real-time PCR mRNA accumulation vivo determined acute lung model.BET inhibition suppressed expression molecules induced TNF-α- LPS, including ICAM-1, VCAM-1 E-selectin, inhibited leukocyte activated HUVEC monolayers. Treatment with JQ1 also attenuated LPS-induced leukocytes endothelial model vivo. Furthermore, reduced activity p38 JNK MAPKs NF-κB TNF-α-stimulated HUVECs. TNF-α-induced activation blocked inhibitors (SB203580) (SP600125).BET important for regulating Strategies targeting may provide new therapeutic approach controlling inflammatory-related diseases.