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首页> 外文期刊>American Journal of Physiology >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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Activation of natural killer cells inhibits liver regeneration in toxin-induced liver injury model in mice via a tumor necrosis factor-alpha-dependent mechanism.

机译:天然杀伤细胞的活化通过肿瘤坏死因子 - α-依赖性机制抑制小鼠毒素诱导的肝损伤模型中的肝再生。

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摘要

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.
机译:肝脏淋巴细胞富含天然杀伤(NK)细胞,并通过注射多胞聚环酸(Poly I:C)的NK细胞通过产生IFN-γ产生部分肝切除模型中的肝再生。然而,NK细胞在四氯化碳模型中肝再生中的NK细胞(CCl(4))诱导的肝损伤仍然未知。在这项研究中,我们研究了CCL(4)模型中肝再生诱导的NK细胞激活的影响。聚I:C抑制CCL(4)-Treated小鼠中的肝再生。 NK细胞的耗尽,但不是Kupffer细胞或T细胞恢复了聚I:C / CCl(4)-Treated小鼠中的肝再生。 poly i:c和ccl(4)Cotreatment协同诱导IFN-gamma和肿瘤坏死因子(TNF)的肝脏和NK细胞产生中NK细胞的积累。在多剂I:C和CCl(4)处理后,这些两种细胞因子的血清水平也是协同诱导的。最后,在聚I:C / CCl(4)-Treated小鼠中堵塞TNF-α但不是IFN-Gamma恢复的肝再生。在一起,这些发现表明,多种I:C治疗通过诱导TNF-α的NK细胞产生抑制CCL(4)诱导的肝损伤模型中的肝再生。

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