CCAAT/enhancer binding protein β expression is increased in the brain during HIV-1-infection and contributes to regulation of astrocyte tissue inhibitor of metalloproteinase-1.
CCAAT/enhancer binding protein β expression is increased in the brain during HIV-1-infection and contributes to regulation of astrocyte tissue inhibitor of metalloproteinase-1.
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在HIV-1感染期间，大脑中CCAAT/增强子结合蛋白β表达增加，并有助于调节金属蛋白酶1的星形胶质细胞组织抑制剂。
DOI：
10.1111/j.1471-4159.2011.07203.x
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发表时间：
2011-07
影响因子：
4.7
通讯作者：
Ghorpade A
中科院分区：
文献类型：
--
作者：
Fields J;Gardner-Mercer J;Borgmann K;Clark I;Ghorpade A
HIV-1相关性神经认知障碍(HAND)与大脑中单核巨噬细胞(MP)的感染和激活有关，发生在疾病的晚期。感染/激活的MP引发神经炎症，激活神经胶质细胞，最终破坏神经元功能。星形胶质细胞在神经损伤时分泌金属蛋白酶组织抑制物(TIMP)-1。TIMP-1水平改变与几种中枢神经系统疾病有关。CCAAT增强子结合蛋白β(C/EBP)是一种转录因子，在啮齿类动物的大脑中被检测到，作为对神经炎症的反应，它与阿尔茨海默氏症、帕金森氏症和艾滋病毒-1相关的神经认知障碍(HAND)有关。在这里，我们报告了C/EBPHIV-1感染和β-1脑炎患者的脑组织裂解物中C/EBP基因表达水平升高及其亚型的差异表达。在体外，手相关刺激通过7天的刺激协同诱导人星形胶质细胞C/eBPβ的核表达。C/eBPβ过表达可增加IL-1β激活的人脑星形胶质细胞中TIMP-1启动子的活性、基因和蛋白水平。用小干扰RNA敲除C/EBPβ可降低TIMP-1mRNA和蛋白水平。这些数据表明，C/EBPβ亚型参与了HIV-1感染期间星形胶质细胞TIMP-1产生的复杂调节；然而，需要进一步研究才能完全了解它们在疾病进展中的作用。
HIV-1-associated neurocognitive disorders (HAND), associated with infection and activation of mononuclear phagocytes (MP) in the brain, occur late in disease. Infected/activated MP initiate neuroinflammation activating glial cells and ultimately disrupting neuronal function. Astrocytes secrete tissue inhibitor of metalloproteinase (TIMP)-1 in response to neural injury. Altered TIMP-1 levels are implicated in several CNS diseases. CCAAT enhancer binding protein β (C/EBP), a transcription factor, is detected in rodent brains in response to neuroinflammation, implicating it in Alzheimer’s, Parkinson’s and HIV-1-associated neurocognitive disorders (HAND). Here, we report that C/EBPβ mRNA levels are elevated and its isoforms differentially expressed in total brain tissue lysates of HIV-1-infected and HIV-1 encephalitis patients. In vitro, HAND-relevant stimuli synergistically induce C/EBPβ nuclear expression in human astrocytes through 7 days of stimulations. Overexpression of C/EBPβ increases TIMP-1 promoter activity, mRNA and protein levels in human astrocytes activated with IL-1β. Knockdown of C/EBPβ with siRNA decreases TIMP-1 mRNA and protein levels. These data suggest C/EBPβ isoforms are involved in complex regulation of astrocyte TIMP-1 production during HIV-1 infection; however, further studies are required to completely understand their role during disease progression.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
11.4
作者：
AKIRA, S;ISSHIKI, H;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
6.2
作者：
Borjabad, Alejandra;Brooks, Andrew I.;Volsky, David J.
通讯作者：
Volsky, David J.
影响因子：
6.1
作者：
Cintia Ferrari, Carina;Pott Godoy, Maria Clara;Juan Pitossi, Fernando
通讯作者：
Juan Pitossi, Fernando
影响因子：
20.3
作者：
Chen, Changyi;Chai, Hong;Yao, Qizhi
通讯作者：
Yao, Qizhi