Ethanol directly induced HMGB1 release through NOX2/NLRP1 inflammasome in neuronal cells. (6th August 2015)

• Record Type: Journal Article
• Authors: Wang, Xiaolan; Chu, Guangpin; Yang, Zhihua; Sun, Yinan; Zhou, Hanjing; Li, Man; Shi, Jing; Tian, Bo; Zhang, Chun; Meng, Xianfang
• Is Part Of: Toxicology. Volume 334(2015)
• Page Start: 104
• Page End: 110
• Publication Date: 2015-08-06
• Subjects: Ethanol -- HMGB1 release -- NOX2 -- NLRP1 inflammasome; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2015.06.006
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: Ethanol directly induced HMGB1 release from neuronal cells. Ethanol-induced HMGB1 release was oxidative stress dependent. NOX2 played an important on in ethanol-induced HMGB1 release. Ethanol induced activation of NLRP1 inflammasomes in neuronal cells. Prevention activation of caspase 1 alleviated HMGB1 release Abstract: It has been reported that ethanol contributes to neuronal damage. However, the mechanisms mediating the actions of ethanol on neurons remain elusive. The present study was designed to test whether ethanol directly induced HMGB1 release and to explore the cellular and molecular mechanism mediating its action. It was found that ethanol increased significant HMGB1 release from SH-SY5Y cells and from cultured primary cortical neurons as detected by ELISA assay. Meanwhile, ethanol induced the expression of NOX2 subunits such as gp91 and p47 phox and increased the activation of NLRP1 inflammasome. However, when cells were pretreated with NADPH oxidase inhibitor, apocynin, HMGB1 release was significantly decreased. Moreover, apocynin also prevented the activation of NLRP1 inflammasome as detected the levels of cleaved caspase-1. In addition, z-YVAD-fmk, an inhibitor of caspase-1, decreased the ethanol-induced HMGB1 release. It is concluded that ethanol-induced HMGB1 release is associated with NOX2/NLRP1 inflammasome signaling, which represents a novel mechanism of ethanol-associated neuron injury.