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Bestrophin 3 ameliorates TNF?-induced inflammation by inhibiting NF-?B activation in endothelial cells.


ABSTRACT: Increasing evidences have suggested vascular endothelial inflammatory processes are the initiator of atherosclerosis. Bestrophin 3 (Best-3) is involved in the regulation of cell proliferation, apoptosis and differentiation of a variety of physiological functions, but its function in cardiovascular system remains unclear. In this study, we investigated the effect of Best-3 on endothelial inflammation. We first demonstrated that Best-3 is expressed in endothelial cells and decreased after tumor necrosis factor-? (TNF?) challenge. Overexpression of Best-3 significantly attenuated TNF?-induced expression of adhesion molecules and chemokines, and subsequently inhibited the adhesion of monocytes to human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of Best-3 with siRNA resulted in an enhancement on TNF?-induced expression of adhesion molecules and chemokines and adhesion of monocytes to HUVECs. Furthermore, overexpression of Best-3 with adenovirus dramatically ameliorated inflammatory response in TNF?-injected mice. Mechanistically, we found up-regulation of Best-3 inhibited TNF?-induced IKK? and I?B? phosphorylation, I?B? degradation and NF-?B translocation. Our results demonstrated that Best-3 is an endogenous inhibitor of NF-?B signaling pathway in endothelial cells, suggesting that forced Best-3 expression may be a novel approach for the treatment of vascular inflammatory diseases.

SUBMITTER: Song W 

PROVIDER: S-EPMC4203846 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Bestrophin 3 ameliorates TNFα-induced inflammation by inhibiting NF-κB activation in endothelial cells.

Song Wei W   Yang Zhen Z   He Ben B  

PloS one 20141020 10


Increasing evidences have suggested vascular endothelial inflammatory processes are the initiator of atherosclerosis. Bestrophin 3 (Best-3) is involved in the regulation of cell proliferation, apoptosis and differentiation of a variety of physiological functions, but its function in cardiovascular system remains unclear. In this study, we investigated the effect of Best-3 on endothelial inflammation. We first demonstrated that Best-3 is expressed in endothelial cells and decreased after tumor ne  ...[more]

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