Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia, and oligodendrocytes grown in culture
Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia, and oligodendrocytes grown in culture
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DOI：
10.1093/jnen/60.4.386
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发表时间：
2001-04-01
影响因子：
3.2
通讯作者：
Kim, SU
中科院分区：
文献类型：
--
作者：
Nagai, A;Nakagawa, E;Kim, SU
促红细胞生成素(EPO)是一种造血生长因子，可刺激红系前体细胞的增殖和分化，并在中枢神经系统(CNS)中发挥神经营养活性。然而，目前对EPO及其受体(EPOR)在人中枢神经系统组织中的表达知之甚少。本研究采用逆转录-聚合酶链式反应(RT-PCR)和酶联免疫吸附试验(ELISA)研究了促炎症细胞因子对高纯度培养的人神经元、星形胶质细胞、小胶质细胞和少突胶质细胞EPO和EPOR表达的影响。EPO mRNA仅在人脑星形胶质细胞中表达，而EPOR在人脑神经元、星形胶质细胞和小胶质细胞中均有表达。少突胶质细胞中未见EPO和EPOR表达。在人类星形胶质细胞中，促炎症细胞因子(IL-1β、IL-6或TNF-α)作用后，EPO mRNA和分泌的EPO蛋白水平下调。在人类神经元中，肿瘤坏死因子-α处理显著增加了EPOR的表达。这些结果表明，促炎细胞因子调节EPO和EPOR在人神经元、星形胶质细胞和小胶质细胞中的表达，并进一步促进人中枢神经系统不同类型细胞之间的相互作用。
Erythropoietin (EPO) is a hematopoietic growth factor that stimulates proliferation and differentiation of erythroid precursor cells and is also known to exert neurotrophic activity in the central nervous system (CNS). However, little is known about expression of EPO and EPO receptor (EPOR) in human CNS tissues. In the present study, we investigated the effects of proinflammatory cytokines on EPO and EPOR expression in highly purified cultures of human neurons, astrocytes, microglia, and oligodendrocytes using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). EPO mRNA was demonstrated only in human astrocytes, while EPOR expression was found in human neurons, astrocytes, and microglia. Neither EPO nor EPOR expression was found in oligodendrocytes. In human astrocytes, EPO mRNA and secreted EPO protein levels were downregulated after exposure to proinflammatory cytokines (IL-1 beta, IL-6, or TNF-alpha). In human neurons, TNF-alpha treatment markedly increased EPOR expression. These results suggest that proinflammatory cytokines regulate expression of EPO and EPOR in human neurons, astrocytes, and microglia and further facilitate interactions among different cell types in the human CNS.