Upregulation of Kupffer cell α2A-Adrenoceptors and downregulation of MKP-1 mediate hepatic injury in chronic alcohol exposure

► Alcohol-induced liver disease is associated with high morbidity and mortality. ► Although chronic alcohol exposure causes norepinephrine (NE) release leading to hepatic injury, the mechanism has not been fully elucidated. ► We induced chronic alcohol conditions in vivo and in vitro and examined the α2A-adrenoceptor mediated hepatic damage. ► Our results showed that chronic alcohol exposure elevates NE and upregulates Kupffer cell α2A-adrenoceptors to release TNF-α. ► Alcohol induced downregulation of MKP-1 leads to further release of TNF-α and hepatic injury.