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摘要
Wei HR, Wei H, Wang H, Tian Z, Sun R. Activation of natural killer cells inhibits liver regeneration in toxin-induced liver injury model in mice via a tumor necrosis factor-alpha-dependent mechanism. Am J Physiol Gastrointest Liver Physiol 299: G275-G282, 2010. First published May 6, 2010; doi:10.1152/ajpgi.00026.2010.-Liver lymphocytes are enriched in natural killer (NK) cells, and activation of NK cells by injection of polyinosinic-polycytidylic acid (poly I:C) inhibits liver regeneration in the partial hepatectomy model via production of IFN-gamma. However, the role of NK cells in liver regeneration in a model of carbon tetrachloride (CCl4)-induced liver injury remains unknown. In this study, we investigated the effect of activation of NK cells induced by poly I: C on liver regeneration in the CCl4 model. Administration of poly I: C suppressed liver regeneration in CCl4-treated mice. Depletion of NK cells but not Kupffer cells or T cells restored liver regeneration in poly I:C/CCl4-treated mice. Poly I:C and CCl4 cotreatment synergistically induced accumulation of NK cells in the liver and NK cell production of IFN-gamma and tumor necrosis factor (TNF)-alpha. Serum levels of these two cytokines were also synergistically induced after poly I: C and CCl4 treatment. Finally, blockage of TNF-alpha but not IFN-gamma restored liver regeneration in poly I:C/CCl4-treated mice. Taken together, these findings suggest that poly I:C treatment inhibits liver regeneration in the CCl4-induced liver injury model via induction of NK cell production of TNF-alpha.
