Immature myeloid cells induced by a high-fat diet contribute to liver inflammation.
Immature myeloid cells induced by a high-fat diet contribute to liver inflammation.
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DOI：
10.1002/hep.23148
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发表时间：
2009-11
期刊：
影响因子：
13.5
通讯作者：
Zhang, Huang-Ge
中科院分区：
文献类型：
--
作者：
Deng, Zhong-bin;Liu, Yuelong;Liu, Cunren;Xiang, Xiaoyu;Wang, Jianhua;Cheng, Ziqiang;Shah, Spandan V.;Zhang, Shuangyin;Zhang, Liming;Zhuang, Xiaoying;Michalek, Sue;Grizzle, William E.;Zhang, Huang-Ge
慢性炎症在促进脂肪肝等肥胖相关疾病中起着至关重要的作用。介导这些作用的炎症细胞仍然未知。这项研究调查了肝脏中未成熟骨髓细胞的积累及其在肝脏炎症中的作用。我们发现，喂食高脂肪饮食的 B6 小鼠肝脏中未成熟骨髓细胞（即 CD11b+Ly6ChiLy6G− 细胞）的积累会导致肝脏炎症。从肥胖 B6 小鼠肝脏（而非瘦 B6 小鼠）分离的 CD11b+Ly6ChiLy6G− 细胞的过继转移会导致肝损伤，这通过血清中肝转移酶活性的增加而明显可见。从肥胖小鼠肝脏中分离出的 CD11b+Ly6ChiLy6G− 细胞更容易通过 Toll 样受体 (TLR) 刺激被激活，导致白细胞介素 12 和其他炎症细胞因子以 MyD88 依赖性方式表达。 TLR7 激活的 CD11b+Ly6ChiLy6G− 细胞也以 Fas 依赖性方式增强肝脏 NKT 细胞死亡。使用去除 Gr-1+ 未成熟骨髓细胞的小鼠进行的实验证明了 CD11b+Ly6ChiLy6G− 在肝脏炎症中的重要作用。重复注射外泌体样颗粒会导致 CD11b+ 细胞激活，随后细胞归巢并在肝脏中积聚。总之，B6 小鼠食用高脂肪饮食会引发肝脏中未成熟骨髓细胞的积累。未成熟的骨髓细胞释放促炎细胞因子并诱导 NKT 细胞凋亡。激活诱导的 NKT 细胞凋亡进一步促进 Th-1 细胞因子的过量产生。这种饮食诱导的未成熟骨髓细胞的积累可能会导致肥胖相关的肝脏疾病。
Chronic inflammation plays a critical role in promoting obesity-related disorders, such as fatty liver disease. The inflammatory cells that mediate these effects remain unknown. This study investigated the accumulation of immature myeloid cells in the liver and their role in liver inflammation. We found that the accumulation of immature myeloid cells, i.e., CD11b+Ly6ChiLy6G− cells, in the liver of B6 mice fed a high-fat diet contribute to liver inflammation. Adoptive transfer of CD11b+Ly6ChiLy6G− cells isolated from the liver of obese B6 mice, but not from lean B6 mice, resulted in liver damage that was evident by an increase in the activity of liver transferases in serum. CD11b+Ly6ChiLy6G− cells isolated from the liver of obese mice are more easily activated via toll-like receptor (TLR) stimulation resulting in interleukin 12 and other inflammatory cytokine expression in a MyD88 dependent fashion. TLR7 activated CD11b+Ly6ChiLy6G− cells also enhance liver NKT cell death in a Fas dependent manner. Experiments using mice depleted of Gr-1+ immature myeloid cells demonstrated the important role of CD11b+Ly6ChiLy6G− in liver inflammation. Repeated injection of exosome-like particles causes CD11b+ cell activation and subsequent homing to and accumulation of the cells in the liver. In conclusion, consumption of a high-fat diet by B6 mice triggers an accumulation of immature myeloid cells in the liver. The immature myeloid cells release proinflammatory cytokines and induce NKT cell apoptosis. Activation induced NKT apoptosis further promotes excessive production of Th-1 cytokines. This diet-induced accumulation of immature myeloid cells may contribute to obesity-related liver disease.
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DOI：
10.1002/hep.22470
发表时间：
2008-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Hritz I;Mandrekar P;Velayudham A;Catalano D;Dolganiuc A;Kodys K;Kurt-Jones E;Szabo G
通讯作者：
Szabo G
影响因子：
6.9
作者：
Vitseva, Olga I.;Tanriverdi, Kahraman;Gokce, Noyan
通讯作者：
Gokce, Noyan
影响因子：
4.4
作者：
Yu, Shaohua;Liu, Cunren;Zhang, Huang-Ge
通讯作者：
Zhang, Huang-Ge
影响因子：
3.7
作者：
Giri PK;Schorey JS
通讯作者：
Schorey JS
DOI：
10.1152/ajpendo.00015.2008
发表时间：
2008-08-01
影响因子：
5.1
作者：
Stadler, Krisztian;Bonini, Marcelo G.;Kadiiska, Maria B.
通讯作者：
Kadiiska, Maria B.