OPIOID MODULATION OF CHEMOKINES AND HIV REPLICATIONS

阿片类药物对趋化因子和 HIV 复制的调节

• 批准号: 2897793
• 负责人: Michele Aileen Kutzler
• 金额: $ 2.02万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2897793
• 关键词: HIV infections; RNase protection assay; T lymphocyte; bioengineering /biomedical engineering; cell line; chemokine; cytokine receptors; endogenous opioid; enzyme linked immunosorbent assay; genetic strain; human immunodeficiency virus 1; immunomodulators; monocyte; polymerase chain reaction; receptor expression; virus replication

DESCRIPTION (Applicant's Abstract): A correlation between HIV-1 infection and intravenous opioid abuse has been established, but the drugs' role in HIV-1 induced disease progression is still uncertain. In addition, alkaloid opiates and endogenous opioid peptides have been shown to alter immune function. Therefore, since opioids can modulate immune activity, there is considerable need to understand the role of opioids in the progress of HIV replication. The current practice of administering opioids as analgesics for treatment of pain in HIV-1 infected individuals and the high risk of HIV infection associated with intravenous drug use suggest the importance of investigating the potential interaction between opioids with HIV-1 infected cells. This proposal seeks to identify the mechanism by which opioids modulate HIV-1 replication and expression, and whether opioids act by modulating the expression of chemokines and their receptors. The proposal will be adressed by the following series of experiements. First, the effects of several selective opioids on the expression of both M-tropic and T-tropic strains of HIV-1 will be examined by reverse trancriptase assay, P24 ELISA, and syncytia counts. Second, T cell lines will be engineered to express opioid receptors to further examine the role of opioid receptors on HIV replication. Lastly, the effects of opioids on the expression of the critical chemokines and chemokine receptors during HIV-1 infection will be measured by RNase protection assay.

描述（申请人的摘要）： HIV-1 感染与静脉注射阿片类药物滥用之间存在相关性 已确定，但这些药物在 HIV-1 诱导的疾病进展中的作用尚不清楚 仍不确定。 此外，阿片生物碱和内源性阿片类药物 肽已被证明可以改变免疫功能。 因此，自从阿片类药物 可以调节免疫活性，因此非常需要了解 阿片类药物在 HIV 复制过程中的作用。 目前的做法是 使用阿片类药物作为止痛药来治疗 HIV-1 感染者的疼痛 个人和与静脉注射相关的艾滋病毒感染高风险 药物使用表明调查潜在相互作用的重要性 阿片类药物与 HIV-1 感染细胞之间的关系。 该提案旨在确定 阿片类药物调节 HIV-1 复制和表达的机制， 以及阿片类药物是否通过调节趋化因子及其表达来发挥作用 受体。 该提案将通过以下一系列措施得到解决 实验。 首先，几种选择性阿片类药物对 将检查 HIV-1 的 M 向性和 T 向性菌株的表达 通过逆转录酶测定、P24 ELISA 和合胞体计数。 二、T 细胞系将被改造为表达阿片受体以进一步检查 阿片受体对 HIV 复制的作用。 最后，效果 阿片类药物对关键趋化因子和趋化因子受体表达的影响 HIV-1感染期间将通过RNase保护测定进行测量。