Tumor necrosis factor-alpha preconditioning attenuates liver ischemia/reperfusion injury through preserving sarco/endoplasmic reticulum calcium-ATPase function.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine. In this study, we investigated the role of TNF-α preconditioning in liver ischemia/reperfusion injury (IRI).

METHODS: After IRI, serum alanine aminotransferase, protein levels of SERCA-3, and Caspase-3 in liver were analyzed. In vitro study, primary hepatocytes were isolated from mice and cultured in hypoxic media with or without TNF-α. The levels of SERCA-3, Caspase-3, and intracellular calcium were evaluated after 24-h incubation. In addition, protease inhibitors were adopted to determine the role of SERCA-3 in TNF-α preconditioning.

RESULTS: Low dose of TNF-α preconditioning protected liver from IRI, which was described by reduced serum alanine aminotransferase, Capase-3, and elevated SERCA-3 compared with the animals without TNF-α treatment. The in vitro test confirmed the protective effect of TNF-α through maintaining homeostasis of intracellular calcium. However, the effect of TNF-α was deprived by protease inhibitors.

CONCLUSIONS: In this study, we demonstrated that IRI reduced SERCA-3 expression in liver. Low dose of TNF-α preconditioning protected against SERCA-3 reducing, promoted intercellular calcium storage, and attenuated liver IRI.