Endothelial Cells Potentiate Interferon-γ Production in a Novel Tripartite Culture Model of Human Cerebral Malaria
Endothelial Cells Potentiate Interferon-γ Production in a Novel Tripartite Culture Model of Human Cerebral Malaria
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DOI：
10.1371/journal.pone.0069521
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发表时间：
2013-07-12
期刊：
影响因子：
3.7
通讯作者：
Hunt, Nicholas H.
中科院分区：
文献类型：
--
作者：
Khaw, Loke Tim;Ball, Helen J.;Hunt, Nicholas H.
为了模拟脑型疟疾（cerebral malaria，CM）的主要病理生理损害，我们建立了人脑内皮细胞（human brain endothelial cells，HBEC）、恶性疟原虫寄生红细胞（Plasmodium falciparum parasitized red blood cells，iRBC）和外周血单个核细胞（peripheral blood mononuclear cells，PBMC）体外共培养体系。这种方法揭示了内皮细胞通过增强PBMC产生干扰素（IFN）-γ和同时减少白细胞介素（IL）-10而发挥的先前未被怀疑的促炎作用。IFN-γ增加了CXCL 10和细胞间粘附分子（ICAM）-1的表达，这两者已被证明在CM的发病机制中是至关重要的。IL-10：IFN-γ蛋白的比例从>1变化到> 10。
We have established a novel in vitro co-culture system of human brain endothelial cells (HBEC), Plasmodium falciparum parasitised red blood cells (iRBC) and peripheral blood mononuclear cells (PBMC), in order to simulate the chief pathophysiological lesion in cerebral malaria (CM). This approach has revealed a previously unsuspected pro-inflammatory role of the endothelial cell through potentiating the production of interferon (IFN)-gamma by PBMC and concurrent reduction of interleukin (IL)-10. The IFN-gamma increased the expression of CXCL10 and intercellular adhesion molecule (ICAM)-1, both of which have been shown to be crucial in the pathogenesis of CM. There was a shift in the ratio of IL-10:IFN-gamma protein from >1 to