Activation of natural killer cells inhibits liver regeneration in toxin-induced liver injury model in mice via a tumor necrosis factor-alpha-dependent mechanism.
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 (CCl(4))-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 CCl(4) model. Administration of poly I:C suppressed liver regeneration in CCl(4)-treated mice. Depletion of NK cells but not Kupffer cells or T cells restored liver regeneration in poly I:C/CCl(4)-treated mice. Poly I:C and CCl(4) 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 CCl(4) treatment. Finally, blockage of TNF-alpha but not IFN-gamma restored liver regeneration in poly I:C/CCl(4)-treated mice. Taken together, these findings suggest that poly I:C treatment inhibits liver regeneration in the CCl(4)-induced liver injury model via induction of NK cell production of TNF-alpha.
Wei
Hairong
H
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 443 Huangshan Rd., Hefei City, Anhui 230027, People's Republic of China.
Wei
Haiming
H
Wang
Hua
H
Tian
Zhigang
Z
Sun
Rui
R
D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002251:Carbon Tetrachloride; D011070:Poly I-C