Dilinoleoylphosphatidylcholine decreases LPS-induced TNF-α generation in Kupffer cells of ethanol-fed rats:: respective roles of MAPKs and NF-κB
Dilinoleoylphosphatidylcholine decreases LPS-induced TNF-α generation in Kupffer cells of ethanol-fed rats:: respective roles of MAPKs and NF-κB
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DOI：
10.1016/s0006-291x(02)00586-7
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发表时间：
2002-06-21
影响因子：
3.1
通讯作者：
Lieber, CS
中科院分区：
文献类型：
--
作者：
Cao, Q;Mak, KM;Lieber, CS
乙醇喂养后，脂多糖（LPS）激活库普弗细胞，导致tnf - α过量产生，导致肝损伤。由于dilinoleoyl磷脂酰胆碱（DLPC）保护肝脏免受损伤并具有抗氧化特性，我们研究了它是否改变脂多糖信号导致tnf - α产生减少。从喂食含酒精或等热量控制饮食的大鼠中分离Kupffer细胞3周。添加乙醇后，细胞色素P4502E1上调。当LPS刺激培养的Kupffer细胞时，与对照大鼠相比，Kupffer细胞释放更多的tnf - α；DLPC抑制了这一增长。它还降低了ERK1/2和p38的磷酸化以及NF-kappaB的活化，降低了核p65，增加了细胞质ikappab - α的表达。ERK1/2抑制剂PD098059可抑制ERK1/2和NF-kappaB的活化。p38抑制剂SB203580在不影响NF-kappaB的情况下抑制p38的活化。两种抑制剂都减少了tnf - α的产生。因此，DLPC通过抑制p38和ERK1/2激活来减少脂多糖依赖性tnf - α的产生；后者导致NF-kappaB活性降低。(C) 2002 Elsevier Science （USA）。版权所有。
Activation of Kupffer cells by lipopolysaccharide (LPS) after ethanol feeding results in overproduction of TNF-alpha, leading to liver injury. Since dilinoleoylphosphatidylcholine (DLPC) protects against liver injury and has antioxidant properties, we investigated whether it alters LPS signaling leading to decreased TNF-alpha production. Kupffer cells were isolated from rats fed alcohol-containing or isocaloric control diets for 3 weeks. With ethanol, cytochrome P4502E1 was upregulated. When stimulated with LPS in culture, Kupffer cells released more TNF-alpha compared to control rats; DLPC diminished the increase. It also reduced ERK1/2 and p38 phosphorylation as well as NF-kappaB activation with decreased nuclear p65 and increased cytosolic IkappaB-alpha expression. ERK1/2 and NF-kappaB activation were abolished by the ERK1/2 inhibitor PD098059. The p38 inhibitor SB203580 abolished p38 activation without affecting NF-kappaB. Both inhibitors reduced TNF-alpha generation. Thus, DLPC diminishes LPS-dependent TNF-alpha generation by inhibiting p38 and ERK1/2 activation; the latter leads to decreased NF-kappaB activation. (C) 2002 Elsevier Science (USA). All rights reserved.