Oxidative products from alcohol metabolism differentially modulate pro-inflammatory cytokine expression in Kupffer cells and hepatocytes.
Oxidative products from alcohol metabolism differentially modulate pro-inflammatory cytokine expression in Kupffer cells and hepatocytes.
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DOI：
10.1016/j.cyto.2016.06.014
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发表时间：
2016-09
期刊：
影响因子：
3.8
通讯作者：
Zhou Z
中科院分区：
文献类型：
--
作者：
Dong D;Zhong W;Sun Q;Zhang W;Sun X;Zhou Z
促炎细胞因子在酒精性脂肪性肝炎的发病机制中起着至关重要的作用。本研究旨在确定酒精诱导的氧化应激在调节细胞因子产生中的作用。采用大鼠饮酒模型测定酒精诱导的肝脏细胞因子表达。长期酒精暴露导致脂质积累，氧化应激和炎症在Wistar大鼠的肝脏。在体外进一步剖析了氧化应激在调节细胞类型特异性细胞因子产生中的作用。脂多糖（LPS）剂量依赖性地上调库普弗细胞SV 40中的TNF-α、MIP-1α、MCP-1和CINC-1，而TNF-α剂量依赖性地诱导H4 IIEC 3肝癌细胞中CINC-1、IP-10和MIP-2的表达。过氧化氢分别与LPS或TNF-α联合作用时，Kupffer细胞SV 40和肝细胞中细胞因子的产生均呈相加效应，这与NF-κB激活和组蛋白H3的高乙酰化有关。出乎意料的是，在LPS处理的Kupffer细胞-SV 40中显示了4-羟基壬烯醛对细胞因子产生的抑制作用。机制研究表明，4-羟基壬烯醛通过降低LPS刺激的Kupffer细胞-SV 40中TNF-α、MCP-1和MIP-1α mRNA结合蛋白的磷酸化水平，促进其mRNA降解，降低MCP-1蛋白水平。这项研究表明，枯否细胞和肝细胞表达不同的促炎细胞因子/趋化因子，响应酒精中毒，和氧化产物（4-羟基壬烯醛）差异调节促炎细胞因子/趋化因子的生产，通过NF-κB信号，组蛋白乙酰化和mRNA的稳定性。
Pro-inflammatory cytokines play a vital role in the pathogenesis of alcoholic steatohepatitis. The present study was to determine the role of alcohol-induced oxidative stress in modulating cytokine production. A rat model of alcohol consumption was used to determine alcohol-induced hepatic cytokine expression. Chronic alcohol exposure caused lipid accumulation, oxidative stress, and inflammation in the livers of Wistar rats. The role of oxidative stress in regulating cell type-specific cytokine production was further dissected in vitro. Lipopolysaccharide (LPS) dose-dependently upregulated TNF-α, MIP-1α, MCP-1, and CINC-1 in Kupffer cells-SV40, whereas TNF-α dose-dependently induced CINC-1, IP-10, and MIP-2 expression in H4IIEC3 hepatoma cells. An addictive effect on cytokine production was observed in both Kupffer cells-SV40 and hepatocytes when combined hydrogen peroxide with LPS or TNF-α, respectively, which was associated with NF-κB activation and histone H3 hyper-acetylation. Unexpectedly, an inhibiting effect of 4-hydroxynonenal on cytokine production was revealed in LPS-treated Kupffer cells-SV40. Mechanistic study showed that 4-hydroxynonenal significantly enhanced mRNA degradation of TNF-α, MCP-1, and MIP-1α, and decreased the protein levels of MCP-1 in LPS-stimulated Kupffer cells-SV40 through reducing the phosphorylation of mRNA binding proteins. This study suggests that Kupffer cells and hepatocytes express distinct pro-inflammatory cytokines/chemokines in response to alcohol intoxication, and oxidative products (4-hydroxynonenal) differentially modulate pro-inflammatory cytokine/chemokine production via NF-κB signaling, histone acetylation, and mRNA stability.
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影响因子：
4.6
作者：
Kawaratani H;Tsujimoto T;Douhara A;Takaya H;Moriya K;Namisaki T;Noguchi R;Yoshiji H;Fujimoto M;Fukui H
通讯作者：
Fukui H
影响因子：
20.1
作者：
Brown, MR;Miller, FJ;Weintraub, NL
通讯作者：
Weintraub, NL
影响因子：
4.1
作者：
ESTERBAUER, H;ZOLLNER, H;LANG, J
通讯作者：
LANG, J
DOI：
10.1111/j.1440-1746.2007.05277.x
发表时间：
2008-03-01
影响因子：
4.1
作者：
De Minicis, Samele;Brenner, David A.
通讯作者：
Brenner, David A.
影响因子：
29.4
作者：
De Minicis, Samuele;Bataller, Ramon;Brenner, David A.
通讯作者：
Brenner, David A.