ATX and LPA receptor 3 are coordinately up-regulated in lipopolysaccharide-stimulated THP-1 cells through PKR and SPK1-mediated pathways
ATX and LPA receptor 3 are coordinately up-regulated in lipopolysaccharide-stimulated THP-1 cells through PKR and SPK1-mediated pathways
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ATX 和 LPA 受体 3 在脂多糖刺激的 THP-1 细胞中通过 PKR 和 SPK1 介导的途径协同上调
DOI：
10.1016/j.febslet.2012.01.044
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发表时间：
2012-03-23
期刊：
影响因子：
3.5
通讯作者：
Zhang, Junjie
中科院分区：
文献类型：
--
作者：
Li, Song;Xiong, Chaoyang;Zhang, Junjie
溶血磷脂酸（LPA）是炎症和免疫中重要的磷脂介质。在此之前，我们发现自分泌运动因子（ATX），即从溶血磷脂酰胆碱（LPC）产生LPA的酶，在THP-1细胞中通过激活PKR、JNK和p38 MAPK被LPS诱导。在本研究中，我们发现ATX和LPA受体3（LPA（3））在LPS刺激的THP-1细胞中协同上调。PKR介导的JNK 1和p38 MAPK活化是ATX和LPA（3）上调所必需的。SPK 1介导的PI 3 K-AKT-β-连环蛋白通路的激活对于ATX诱导是必需的，而SPK 1介导的ERK激活对于LPA（3）上调是必需的。ATX或LPA（3）敲低均抑制LPS诱导的CCL 8诱导，表明ATX和LPA（3）在对抗细菌感染的炎症过程中参与CCL 8诱导。(C)2012年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. Previously, we showed that autotaxin (ATX), the enzyme producing LPA from lysophosphatidylcholine (LPC), is induced by LPS in THP-1 cells via the activation of PKR, JNK and p38 MAPK. In this study, we find that ATX and LPA receptor 3 (LPA(3)) are coordinately up-regulated in LPS-stimulated THP-1 cells. PKR-mediated activation of JNK1 and p38 MAPK is required for both ATX and LPA(3) up-regulation. SPK1-mediated activation of the PI3K-AKT-beta-catenin pathway is essential for ATX induction, while SPK1-mediated ERK activation is required for LPA(3) up-regulation. Either ATX or LPA(3) knock-down inhibited CCL8 induction by LPS, suggesting that ATX and LPA(3) are involved in CCL8 induction during the inflammatory process against bacterial infection. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.