Activation of natural killer cells inhibits liver regeneration in toxin-induced liver injury model in mice via a tumor necrosis factor-alpha-dependent mechanism.
Activation of natural killer cells inhibits liver regeneration in toxin-induced liver injury model in mice via a tumor necrosis factor-alpha-dependent mechanism.
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DOI：
10.1152/ajpgi.00026.2010
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发表时间：
2010-07
期刊：
影响因子：
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通讯作者：
Hairong Wei;Haiming Wei;Hua Wang;Z. Tian;R. Sun
中科院分区：
文献类型：
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作者：
Hairong Wei;Haiming Wei;Hua Wang;Z. Tian;R. Sun
肝淋巴细胞富含自然杀伤（NK）细胞，通过注射聚肌胞苷酸（poly I：C）激活NK细胞可通过产生IFN-γ抑制部分肝切除术模型中的肝再生。然而，在四氯化碳（CCl（4））诱导的肝损伤模型中，NK细胞在肝再生中的作用仍然未知。在本研究中，我们研究了由poly I：C诱导的NK细胞活化对CCl（4）模型中的肝再生的影响。在CCl（4）处理的小鼠中，给予poly I：C抑制肝再生。在poly I：C/CCl（4）处理的小鼠中，NK细胞而非枯否细胞或T细胞的耗竭恢复了肝再生。Poly I：C和CCl（4）共处理协同诱导NK细胞在肝脏中的积聚以及NK细胞产生IFN-γ和肿瘤坏死因子（TNF）-α。在poly I：C和CCl（4）处理后，这两种细胞因子的血清水平也被协同诱导。最后，阻断TNF-α而不是IFN-γ可以恢复poly I：C/CCl（4）治疗小鼠的肝再生。综上所述，这些发现表明聚I：C处理通过诱导NK细胞产生TNF-α来抑制CCl（4）诱导的肝损伤模型中的肝再生。
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.