NFKB ACTIVATION IN PNEUMOCOCCUS AND SIV-COINFECTED LUNGS

肺炎球菌和 SIV 合并感染的肺部中 NFKB 激活

• 批准号: 7349002
• 负责人: GREGORY JOHN BAGBY
• 金额: $ 6.54万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349002
• 关键词: NFKB; ACTIVATION; PNEUMOCOCCUS; SIV; COINFECTED

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Simian Immunodeficiency Virus (SIV) infection of macaques is an important animal model for the acquired immunodeficiency syndrome (AIDS) that recapitulates most features of HIV infection, including CNS disease. Alcohol has been shown to exacerbate other disease states, notably pneumonia. Activation of NFKB is known to be an initial step in the development of disease. To determine if SIV infection of macaques exacerbates the activation of NFKB and its subsequent translocation from the cytoplasm to the perinuclear area we obtained bronchoalveolar lavage (BAL) fluids from rhesus macaques before and after infection with pneumococcus. We also examined lung tissues obtained from the same macaques at necropsy. In situ hybridization and immunohistochemistry was performed on these tissues to determine if there is colocaliztion of the virus and NFKB within nucleus of cells. In addition to increased expression in type II pneumocytes, NFKB was activated in SIV-infected macrophages and also in adjacent macrophages that have recently migrated into lungs in response to pneumococcus challenge. These experiments can be only performed in the rhesus macaque model due to obtaining samples before infection with SIV and at timed intervals thereafter. Immunohistochemistry and in situ hybridization indicate that inoculation of an SIV-infected macaque with pneumococcus leads to an increase in NFKB activation and increased numbers of SIV-infected cells within the lungs when compared with cells derived from the same lung in the same animal previously.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。猴免疫缺陷病毒(SIV)感染猕猴是获得性免疫缺陷综合征(AIDS)的重要动物模型，它概括了HIV感染的大部分特征，包括中枢神经系统疾病。酒精已被证明会加重其他疾病状态，特别是肺炎。NFKB的激活被认为是疾病发展的第一步。为了确定SIV感染猕猴是否会加剧NFKB的激活以及随后NFKB从细胞质转移到核周区域，我们从感染肺炎球菌前后猕猴的支气管肺泡灌洗液(BAL)中获取了NFKB的活性。我们还在尸检时检查了从相同猕猴身上获得的肺组织。对这些组织进行原位杂交和免疫组织化学染色，以确定病毒与NFKB在细胞核内是否共存。除了在II型肺泡细胞中表达增加外，NFKB在SIV感染的巨噬细胞以及最近因肺炎球菌攻击而迁移到肺内的邻近巨噬细胞中也被激活。这些实验只能在恒河猴模型中进行，因为在感染SIV之前和之后每隔一定时间获取样本。免疫组织化学和原位杂交显示，与来自同一动物的同一肺来源的细胞相比，感染SIV的猕猴接种肺炎球菌后，肺内NFKB活性和SIV感染细胞数量增加。