Dilinoleoylphosphatidylcholine decreases acetaldehyde-induced TNF-α generation in Kupffer cells of ethanol-fed rats
Dilinoleoylphosphatidylcholine decreases acetaldehyde-induced TNF-α generation in Kupffer cells of ethanol-fed rats
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DOI：
10.1016/s0006-291x(02)02672-4
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发表时间：
2002-12-06
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
我们之前报道过，dilinoleoyl磷脂酰胆碱（DLPC）通过阻断p38、ERK1/2和NF-kappaB的激活，降低脂多糖诱导的乙醇饲养大鼠Kupffer细胞的tnf - α生成。在这里，我们表明DLPC也降低了乙醛对tnf - α的诱导，乙醛是乙醇氧化释放的一种有毒代谢物。乙醛诱导tnf - α生成，在200 muM时效果最大，并激活p38和ERK1/2；后者反过来激活NF-kappaB，这种作用在乙醇喂养大鼠的Kupffer细胞中增强，乙醇上调细胞色素P4502E1。DLPC通过阻断p38、ERK1/2和NF-kappaB激活来减少tnf - α的产生。同样，SB203580和PD098059可以抑制p38的活化，而PD098059可以抑制ERK1/2和NF-kappaB的活化，从而减少tnf - α的产生。由于增加的TNF-a生成在酒精性肝病中起致病作用，DLPC对Kupffer细胞的作用可以部分解释其对乙醇消耗后肝细胞损伤的有益作用。(C) 2002 Elsevier Science （USA）。版权所有。
We previously reported that dilinoleoylphosphatidylcholine (DLPC) decreases lipopolysaccharide-induced TNF-alpha generation by Kupffer cells of ethanol-fed rats by blocking p38, ERK1/2, and NF-kappaB activation. Here we show that DLPC also decreases TNF-alpha induction by acetaldehyde, a toxic metabolite released by ethanol oxidation. Acetaldehyde induces TNF-alpha generation with a maximal effect at 200 muM and activates p38 and ERK1/2; the latter in turn activates NF-kappaB This effect is augmented in Kupffer cells of ethanol-fed rats, with upregulation of cytochrome P4502E1 by ethanol. DLPC decreases TNF-alpha generation by blocking p38, ERK1/2, and NF-kappaB activation. Likewise, SB203580, which abolishes p38 activation, and PD098059, which abrogates ERK1/2 and NF-kappaB activation, diminish TNF-alpha generation. Since increased TNF-a generation plays a pathogenic role in alcoholic liver disease, the DLPC action on Kupffer cells may explain, in part, its beneficial effects on liver cell injury after ethanol consumption. (C) 2002 Elsevier Science (USA). All rights reserved.