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Clinical immunology (Orlando, Fla.)

High-mobility group box 1 exacerbates CCl₄-induced acute liver injury in mice.


PMID 24726765

Abstract

High-mobility group box 1 (HMGB1) is a nuclear factor that can also serve as an imflammatory mediator once released into extracellular milieu. Therefore, HMGB1 has been recognized to play a pivotal role in inflammatory diseases such as sepsis, acute lung injury, ischemia reperfusion injury and type 1 diabetes. Nevertheless, its impact on carbon tetrachloride (CCl4)-induced hepatic injury is yet to be elucidated. In the present report, we demonstrated evidence indicating that high levels of HMGB1 were not only present in the necrotic area of liver but also in the serum after CCl4 challenge. In line with these observations, administration of exogenous recombinant HMGB1 exacerbated CCl4-induced hepatic injury, while HMGB1 blocking antibody provided protection for mice against CCl4-induced acute liver injury as evidenced by the decrease of serum transaminase and reduction of hepatic tissues necrosis. Mechanistic studies revealed that blockade of HMGB1 attenuated CCl4-induced MDA accumulation along with improved SOD and GSH activity. Treatment of mice with HMGB1 neutralizing antibody also significantly inhibited the production of proinflammatory mediators TNF-α and IL-6 along with attenuated HMGB1 expression and its extracellular release. Together, our data suggest an essential role for HMGB1 in CCl4-induced acute liver injury, while HMGB1 neutralizing antibody could be served as an effective regimen for preventing CCl4-induced acute liver injury.