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: 2710711
• 负责人: Michele Aileen Kutzler
• 金额: $ 1.75万
• 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: 1999-02-27 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2710711
• 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的相关性已经存在 已建立，但是药物在HIV-1诱导疾病进展中的作用是 仍然不确定。 另外，生物碱阿片类药物和内源性阿片类药物 肽已被证明可以改变免疫功能。 因此，由于阿片类药物 可以调节免疫活动，很需要了解 阿片类药物在艾滋病毒复制进展中的作用。 当前的做法 将阿片类药物作为镇痛药，以治疗感染HIV-1的疼痛 个体和静脉内艾滋病毒感染的高风险 使用药物表明研究潜在相互作用的重要性 在患有HIV-1感染细胞的阿片类药物之间。 该建议旨在确定 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的表达及其作用 受体。 该提案将受到以下一系列的尊重 经验。 首先，几种选择性阿片类药物对 将检查HIV-1的M-热带和T-热带菌株的表达 通过反向trancriptase分析，p24 ELISA和合成曲霉计数。 第二，t 细胞系将设计以表达阿片类药物受体以进一步检查 阿片受体在HIV复制中的作用。 最后，影响 关于临界趋化因子和趋化因子受体表达的阿片类药物 HIV-1感染期间将通过RNase保护测定法测量。