Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease
Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease
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DOI：
10.1016/j.cyto.2016.01.020
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发表时间：
2016-06-01
期刊：
影响因子：
3.8
通讯作者：
Ramanathan, Sheela
中科院分区：
文献类型：
--
作者：
Cepero-Donates, Yuneivy;Lacraz, Gregory;Ramanathan, Sheela
白细胞介素-15（IL-15）对于淋巴细胞特别是记忆性CD8（+）T细胞和NK细胞的稳态是必需的。这些细胞在肝脏中大量存在，并与肥胖相关的致病过程有关。在这里，我们描述了缺乏IL-15或IL-15R α的小鼠肝脏中与肥胖相关的代谢和细胞变化。在IL-15或IL-15R α缺陷小鼠的肝脏中，高脂饮食诱导的脂质积累减少。参与肝脏脂质转运的酶的表达显示出适度的差异。更引人注目的是，IL 15-KO和IL 15 R alpha-KO小鼠的肝脏组织显示趋化因子CCI2、CCL 5和CXCL 10的表达减少，单核细胞的浸润减少。在体外，IL-15刺激诱导野生型肝细胞中的趋化因子基因表达，但在IL-15 R α缺陷型肝细胞中不诱导。我们的研究结果表明，IL-15与高脂饮食诱导的肝脏脂质积聚和炎症有关，导致脂肪肝疾病。(C)2016爱思唯尔有限公司版权所有
Interleukin-15 (IL-15) is essential for the homeostasis of lymphoid cells particularly memory CD8(+) T cells and NK cells. These cells are abundant in the liver, and are implicated in obesity-associated pathogenic processes. Here we characterized obesity-associated metabolic and cellular changes in the liver of mice lacking IL-15 or IL-15R alpha. High fat diet-induced accumulation of lipids was diminished in the livers of mice deficient for IL-15 or IL-15R alpha. Expression of enzymes involved in the transport of lipids in the liver showed modest differences. More strikingly, the liver tissues of IL15-KO and IL15R alpha-KO mice showed decreased expression of chemokines CCI2, CCL5 and CXCL10 and reduced infiltration of mononuclear cells. In vitro, IL-15 stimulation induced chemokine gene expression in wildtype hepatocytes, but not in IL15R alpha-deficient hepatocytes. Our results show that IL-15 is implicated in the high fat diet-induced lipid accumulation and inflammation in the liver, leading to fatty liver disease. (C) 2016 Elsevier Ltd. All rights reserved.