cPLA2α-mediated actin rearrangements downstream of the Akt signaling is required for Cronobacter sakazakii invasion into brain endothelial cells
cPLA2α-mediated actin rearrangements downstream of the Akt signaling is required for Cronobacter sakazakii invasion into brain endothelial cells
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DOI：
10.1016/j.bbrc.2011.11.079
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发表时间：
2012-01-20
影响因子：
3.1
通讯作者：
Chen, Yu-Hua
中科院分区：
文献类型：
--
作者：
Liu, Dong-Xin;Zhao, Wei-Dong;Chen, Yu-Hua
阪崎慢杆菌(C sakazakii，C sakazakii)是引起新生儿败血症和脑膜炎的一种条件致病菌。阪崎肠杆菌脑膜炎发病的分子机制尚不清楚。在本研究中，我们发现经胞浆磷脂酶A(2)α(CPLA(2)α)抑制剂处理的人脑微血管内皮细胞(HBMEC)侵袭力显著降低。在感染阪崎肠杆菌的HBMEC中观察到CPLA(2)α的磷酸化增加，这一作用可被CPLA(2)α抑制剂阻止。HBMEC中Cpla(2)α基因敲除可显著减弱阪崎肠杆菌对HBMEC的侵袭。免疫荧光显示，Cpla(2)α抑制剂或Cpla(2)αsiRNA均能有效地阻断CpLA(2)α抑制剂或Cpla(2)αsiRNA对CpLA(2)诱导的HBMEC肌动蛋白微丝重排的影响。有趣的是，我们发现Sakazakii感染促进了磷酸化的CPLA(2)α的聚集，这与HBMEC中解聚的肌动蛋白细丝有关。此外，我们的数据显示，Cpla(2)α作用于Sakazakii刺激的HBMEC Akt信号通路的下游。综上所述，我们的结果表明，Cpla(2)α介导的肌动蛋白细丝重排在Akt激活下游是Sakazakii侵袭脑内皮细胞所必需的。皇冠版权所有(C)2011由爱思唯尔公司出版。保留所有权利。
Cronobacter sakazakii (C sakazakii) is an opportunistic pathogen that causes sepsis and meningitis in neonate. The molecular mechanism involved in the pathogenesis of C sakazakii meningitis remains unclear. In this study, we found that C. sakazakii invasion was significantly decreased in human brain microvascular endothelial cells (HBMEC) treated with cytosolic phospholipases A(2)alpha (cPLA(2)alpha) inhibitor. Increased phosphorylation of cPLA(2)alpha was observed in HBMEC infected with C sakazakii, which was prevented by treatment with cPLA(2)alpha inhibitor. cPLA(2)alpha knockdown in HBMEC significantly attenuated C sakazakii invasion into HBMEC. Immunofluorescence demonstrated that the rearrangements of actin filaments in HBMEC induced by C. sakazakii were effectively blocked by either treatment with cPLA(2)alpha inhibitor or transfection with cPLA(2)alpha siRNA. Interestingly, we found that C sakazakii infection promoted the aggregation of phosphorylated cPLA(2)alpha, which was associated with depolymerized actin filaments in HBMEC. Furthermore, our data revealed that cPLA(2)alpha acts downstream of Akt signaling pathway in HBMEC stimulated with C sakazakii. Taken together, our results illustrated that cPLA(2)alpha-mediated actin filament rearrangements downstream of Akt activation is required for C. sakazakii invasion into brain endothelial cells. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.