An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: regulation of proinflammatory cytokines and hepatic steatosis in mice.
An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: regulation of proinflammatory cytokines and hepatic steatosis in mice.
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单核细胞趋化蛋白-1在酒精性肝损伤中的重要作用：对小鼠促炎细胞因子和肝脂肪变性的调节
DOI：
10.1002/hep.24599
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发表时间：
2011-12
期刊：
影响因子：
13.5
通讯作者：
Catalano, Donna
中科院分区：
文献类型：
--
作者：
Mandrekar, Pranoti;Ambade, Aditya;Lim, Arlene;Szabo, Gyongyi;Catalano, Donna
趋化因子在酒精性肝损伤中的重要性已被牵连。趋化因子单核细胞趋化蛋白-1（MCP-1）升高在酒精性肝病患者中的作用尚不清楚。本文旨在探讨MCP-1及其受体CCR 2在酒精性肝损伤中的病理生理意义。将含有酒精的Leiber-DeCarli饮食或等热量对照饮食饲喂野生型（WT）和MCP-1缺陷型（KO）小鼠5周。进行体内和体外测定以研究MCP-1在酒精性肝损伤中的作用。MCP-1在库普弗细胞以及酒精喂养小鼠的肝细胞中增加。在WT和CCR 2KO小鼠中，酒精喂养增加了血清ALT，但MCP-1 KO小鼠没有。酒精诱导的肝脏脂肪变性和甘油三酯在酒精喂养的MCP-1 KO中减弱，但与WT相比，CCR 2KO中较高，而在酒精喂养的WT和MCP-1 KO小鼠中血清内毒素较高。在酒精喂养的WT小鼠中，肝脏促炎细胞因子TNFα、IL-1β、IL-6、KC/IL-8、ICAM-1和CD 68的表达被诱导，但在MCP-1 KO中被抑制，不依赖于Kupffer细胞中NFκB的激活。与WT相比，在长期酒精喂养的MCP-1 KO小鼠中，氧化应激（但非CYP 2 E1）得到预防。与WT对照组相比，在酒精喂养的MCP-1 KO小鼠肝脏中，PPARα和PPARγ的表达增加，伴有核转位、DNA结合和脂肪酸代谢基因ACOX和CPT-1的诱导。体外试验发现，重组MCP-1对肝细胞中的PPARα mRNA和PPRE结合具有抑制作用，与CCR 2无关。MCP-1的缺乏保护小鼠免受酒精性肝损伤，独立于CCR 2，通过抑制促炎细胞因子和诱导与脂肪酸氧化相关的基因，将趋化因子与肝脏脂质代谢联系起来。
The importance of chemokines in alcoholic liver injury has been implicated. The role of chemokine, monocyte chemoattractant protein-1 (MCP-1) elevated in patients with alcoholic liver disease is not yet understood. Here we evaluate the pathophysiological significance of MCP-1 and its receptor CCR2 in alcoholic liver injury. Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1 deficient (KO) mice for 5 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells as well as hepatocytes of alcohol-fed mice. Alcohol feeding increased serum ALT, in WT and CCR2KO but not MCP-1KO mice. Alcohol-induced liver steatosis and triglyceride was attenuated in alcohol-fed MCP-1KO but high in CCR2KO compared to WT, whereas serum endotoxin was high in alcohol-fed WT and MCP-1KO mice. Expression of liver pro-inflammatory cytokines TNFα, IL-1β, IL-6, KC/IL-8, ICAM-1 and CD68 was induced in alcohol-fed WT mice but inhibited in MCP-1KO, independent of NFκB activation in Kupffer cells. Oxidative stress, but not CYP2E1, was prevented in chronic alcohol-fed MCP-1KO mice compared to WT. Increased expression of PPARα and PPARγ, was accompanied by nuclear translocation, DNA binding and induction of fatty acid metabolism genes, ACOX and CPT-1, in livers of alcohol-fed MCP-1KO mice compared to WT controls. In vitro assays uncovered an inhibitory effect of recombinant MCP-1 on PPARα mRNA and PPRE binding in hepatocytes, independent of CCR2. Deficiency of MCP-1 protects mice against alcoholic liver injury, independent of CCR2, by inhibition of pro-inflammatory cytokines and induction of genes related to fatty acid oxidation, linking chemokines to hepatic lipid metabolism.
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影响因子：
4.3
作者：
Mandrekar, Pranoti
通讯作者：
Mandrekar, Pranoti
影响因子：
4.4
作者：
Ajuebor, MN;Hogaboam, CM;Swain, MG
通讯作者：
Swain, MG
影响因子：
3.6
作者：
Maitra U;Chang S;Singh N;Li L
通讯作者：
Li L
影响因子：
7.7
作者：
Obstfeld AE;Sugaru E;Thearle M;Francisco AM;Gayet C;Ginsberg HN;Ables EV;Ferrante AW Jr
通讯作者：
Ferrante AW Jr
DOI：
10.4049/jimmunol.0803206
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mandrekar P;Bala S;Catalano D;Kodys K;Szabo G
通讯作者：
Szabo G