Rosiglitazone modulates the innate immune response to Plasmodium falciparum infection and improves outcome in experimental cerebral malaria.
Rosiglitazone modulates the innate immune response to Plasmodium falciparum infection and improves outcome in experimental cerebral malaria.
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罗格列酮调节对恶性疟原虫感染的先天免疫反应，并改善实验性脑型疟疾的治疗结果。
DOI：
10.1086/598222
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kain,KevinC
中科院分区：
文献类型：
--
作者：
Serghides,Lena;Patel,SamirN;Ayi,Kodjo;Lu,Ziyue;Gowda,DChanne;Liles,WConrad;Kain,KevinC
对于脑型疟疾等严重疟疾综合征，不良临床结果往往由免疫系统介导，而不是由寄生虫直接引起。然而，很少有治疗药物被开发来调节宿主对感染的免疫病理反应。在这里，我们报道过氧化物酶体增殖物激活受体γ (PPARγ)激动剂罗格列酮通过抑制恶性疟原虫糖基磷脂酰肌醇诱导的丝裂原活化蛋白激酶（MAPK）和核因子-κB （NF-κB）信号通路的激活，增强疟疾寄生红细胞的吞噬清除，降低感染的炎症反应，从而调节宿主对疟疾的反应。我们发现，在贝格氏疟原虫ANKA脑型疟疾实验模型中，罗格列酮可以改变疟疾感染的炎症反应，即使在感染后5天才开始治疗，也能提高生存率。此外，罗格列酮在chabaudi疟原虫高寄生虫血症模型中以cd36依赖的方式降低寄生虫血症。这些数据表明，PPARγ激动剂代表了一类新的宿主免疫调节药物，可能对治疗严重疟疾综合征有用
For severe malarial syndromes such as cerebral malaria, adverse clinical outcomes are often mediated by the immune system rather than caused by the parasite directly. However, few therapeutic agents have been developed to modulate the host’s immunopathological responses to infection. Here, we report that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone modulated the host response to malaria by enhancing phagocytic clearance of malaria-parasitized erythrocytes and by decreasing inflammatory responses to infection via inhibition ofPlasmodium falciparumglycosylphosphatidylinositol-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor–κB (NF-κB) signaling pathways. We found that, in thePlasmodium bergheistrain ANKA experimental model of cerebral malaria, rosiglitazone modified the inflammatory response to malarial infection and improved the survival rate even when treatment was initiated as late as day 5 after infection. Furthermore, rosiglitazone reduced the parasitemia in a CD36-dependent manner in thePlasmodium chabaudi chabaudihyperparasitemia model. These data suggest that PPARγ agonists represent a novel class of host immunomodulatory drugs that may be useful for treatment of severe malaria syndromes
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居住在肯尼亚西部疟疾肆虐地区的儿童中，白细胞介素 10 肿瘤坏死因子-α 比率较低与疟疾贫血有关。
影响因子：
6.4
作者：
C. Othoro;Altaf A. Lal;Bernard L. Nahlen;Davy K. Koech;A. S. Orago;V. Udhayakumar
通讯作者：
V. Udhayakumar
影响因子：
6.4
作者：
Wassmer, SC;Lépolard, C;Grau, GE
通讯作者：
Grau, GE
影响因子：
64.8
作者：
Aitman, TJ;Cooper, LD;Scott, J
通讯作者：
Scott, J
影响因子：
4.4
作者：
Serghides, L;Kain, KC
通讯作者：
Kain, KC
DOI：
--
发表时间：
1998
期刊：
The Lancet
影响因子：
--
作者：
N. White
通讯作者：
N. White