Unmasking of LPA(1)receptor-mediated migration response to lysophosphatidic acid by interleukin-1β-induced attenuation of Rho signaling pathways in rat astrocytes
Unmasking of LPA(1)receptor-mediated migration response to lysophosphatidic acid by interleukin-1β-induced attenuation of Rho signaling pathways in rat astrocytes
复制标题
通过白介素-1β诱导的大鼠星形胶质细胞中 Rho 信号通路的减弱，揭示 LPA(1) 受体介导的对溶血磷脂酸的迁移反应
DOI：
10.1111/j.1471-4159.2011.07188.x
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发表时间：
2011
期刊：
影响因子：
4.7
通讯作者：
Sato K
中科院分区：
文献类型：
--
作者：
Kitamura H;Makide K;Shuto A;Ikubo M;Inoue A;Suzuki K;Sato Y;Nakamura S;Otani Y;Ohwada T;Aoki J;Kazushi Mashima;Shiro Saka;竹内洋文;Sato K
神经化学杂志。（2011）117，164- 174.摘要在大鼠星形胶质细胞中研究了脂多糖（LPS）、白细胞介素-1 β（IL-1β）和溶血磷脂酸（LPA）调节运动性（星形胶质细胞增生的重要过程）的作用机制。虽然LPA对细胞迁移没有显著影响，但用LPS或IL-1β预先处理细胞导致出现响应LPA的迁移活性。LPS诱导对LPA的迁移反应与IL-1β前体蛋白的产生有关，并被IL-1受体拮抗剂抑制。IL-1β治疗还允许LPA激活Rac 1。LPA诱导的Rac 1激活和迁移可被百日咳毒素（一种对LPA 1受体特异性的小干扰RNA）和LPA 1受体拮抗剂（包括Ki 16425）抑制。然而，IL-1β处理对LPA 1受体mRNA表达和LPA诱导的ERK、Akt活化和增殖无明显影响。IL-1β诱导的对LPA的迁移反应被组成型活性RhoA抑制。此外，在对照细胞中，LPA通过LPA 1受体显著激活RhoA，而在IL-1β处理的细胞中则没有。这些结果表明，IL-1β通过IL-1受体抑制LPA 1受体介导的Rho信号传导，从而揭示了LPA 1受体介导的Giprotein/Rac/迁移途径。
J. Neurochem.(2011)117, 164–174.AbstractAction mechanism of lipopolysaccharide (LPS), interleukin‐1β (IL‐1β), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL‐1β resulted in the appearance of migration activity in response to LPA. The LPS induction of the migration response to LPA was associated with the production of IL‐1β precursor protein and inhibited by the IL‐1 receptor antagonist. The IL‐1β treatment also allowed LPA to activate Rac1. The LPA‐induced Rac1 activation and migration were inhibited by pertussis toxin, a small interfering RNA specific to LPA1receptors, and LPA1receptor antagonists, including Ki16425. However, the IL‐1β treatment had no appreciable effect on LPA1receptor mRNA expression and LPA‐induced activation of ERK, Akt, and proliferation. The induction of the migration response to LPA by IL‐1β was inhibited by a constitutively active RhoA. Moreover, LPA significantly activated RhoA through the LPA1receptor in the control cells but not in the IL‐1β‐treated cells. These results suggest that IL‐1β inhibits the LPA1receptor‐mediated Rho signaling through the IL‐1 receptor, thereby disclosing the LPA1receptor‐mediated Giprotein/Rac/migration pathway.