CMV-INFECTED ASTROCYTES PRODUCE TGF-BETA

CMV 感染的星形细胞产生 TGF-β

• 批准号: 3792532
• 负责人: J F MANISCHEWITZ
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792532
• 关键词: adult human (21+); astrocytes; cytomegalovirus; encephalitis; human subject; human tissue; immunoperoxidase; laboratory mouse; messenger RNA; nervous system disorder; secretory protein; stainings; tissue /cell culture; transforming growth factors; virus infection mechanism

CMV infection of the central nervous system in immunocompromised adults, such as AIDS patients, can cause devastating neuropathology. Since cytokines play a pivotal role in inflammatory responses and may be important mediators of central nervous system dysfunction, we investigated the role of transforming growth factor (TGF-Beta) in the pathogenesis of CMV encephalopathy. Brain tissue from AIDS patients with CMV cerebritis, but not normal subjects, contained TGF-beta detected by immunoperoxidase staining. TGF-beta staining could be localized within or near astrocytes, some of which were infected with CMV. To determine whether CMV infection of astrocytes could induce production of TGF-beta, we incubated murine astrocytes with murine CMV in vitro. The infected astrocytes were assayed for TGF-beta mRNA, and the astrocyte culture supernatants were assayed for CMV and TGF-beta. It was found that the astrocytes were productively infected with the murine CMV, expressed TGF-beta mRNA, and secreted TGF-beta peptide.

免疫功能低下的成人中枢神经系统CMV感染， 如艾滋病患者，可能导致毁灭性的神经病理学。以来 细胞因子在炎症反应中起关键作用， 中枢神经系统功能障碍的重要介质，我们 研究了转化生长因子（TGF-β）在 CMV脑病的发病机制。艾滋病患者的脑组织 CMV脑炎，而不是正常受试者，含有TGF-β检测 免疫过氧化物酶染色。TGF-β染色可定位于 或者靠近星形胶质细胞，其中一些被CMV感染。以确定 星形胶质细胞的CMV感染是否可以诱导TGF-β的产生， 我们在体外用鼠CMV孵育鼠星形胶质细胞。受感染的 检测星形胶质细胞的TGF-β mRNA，星形胶质细胞培养物 测定上清液的CMV和TGF-β。发现该 星形胶质细胞用鼠CMV进行生产性感染，表达 TGF-β mRNA和分泌的TGF-β肽。