HDAC6 Inhibition Prevents TNF-α-Induced Caspase 3 Activation in Lung Endothelial Cell and Maintains Cell-Cell Junctions

Authors

Jinyan Yu, University of KentuckyFollow
Mengshi Ma, University of KentuckyFollow
Zhongsen Ma, The Second Hospital of Jilin University, China
Jian Fu, University of KentuckyFollow

Abstract

Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of HDAC6 expression was able to prevent caspase 3 activation in lung endothelial cells and maintain lung endothelial cell-cell junctions. Mice pre-treated with HDAC6 inhibitors exhibited decreased endotoxin-induced caspase 3 activation and reduced lung vascular injury as indicated by the retention of cell-cell junction protein VE-Cadherin level and alleviated lung edema. Collectively, our data suggest that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells.

Document Type

Article

Publication Date

7-13-2016

Notes/Citation Information

Published in Oncotarget, v. 7, no. 34, p. 54714-54722.

Licensed under a Creative Commons Attribution 3.0 License.

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.10591

Funding Information

Jinyan Yu is a recipient of the State Scholarship from China Scholarship Council.

Repository Citation

Yu, Jinyan; Ma, Mengshi; Ma, Zhongsen; and Fu, Jian, "HDAC6 Inhibition Prevents TNF-α-Induced Caspase 3 Activation in Lung Endothelial Cell and Maintains Cell-Cell Junctions" (2016). Center for Research on Environmental Disease Faculty Publications. 6.
https://uknowledge.uky.edu/environmental_disease_facpub/6