Coordinate cytokine gene expression in vivo following induction of tuberculous pleurisy in guinea pigs
Coordinate cytokine gene expression in vivo following induction of tuberculous pleurisy in guinea pigs
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DOI：
10.1128/iai.71.8.4271-4277.2003
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发表时间：
2003-08-01
影响因子：
3.1
通讯作者：
McMurray, DN
中科院分区：
文献类型：
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作者：
Allen, SS;McMurray, DN
结核性胸膜炎是由肺肉芽肿逃逸的结核分枝杆菌引起的严重炎症反应。肺部感染时进入胸腔。我们使用豚鼠结核性胸膜炎模型来检查对这种抗原特异性炎症事件的免疫反应的几个方面。将热灭活的结核分枝杆菌H37Rv直接注射到先前接种过牛分枝杆菌卡介苗的豚鼠胸膜间隙中，引起胸膜炎。在9天的时间里，每天对4只动物实施安乐死。分析胸腔内液体转化生长因子PI （tgf - β 1）和总干扰素（IFN）蛋白水平。此外，从胸膜细胞中提取RNA，并通过实时PCR检测tgf - β 1、肿瘤坏死因子α (tnf - α)、ifn - γ和白细胞介素8 （IL-8）的表达。最后，我们在体外检测了胸膜细胞对刀豆蛋白A和纯化蛋白衍生物（PPD）的增殖能力。在胸膜液中，tgf - β 1蛋白浓度在炎症反应过程中升高，而IFN蛋白水平没有显著改变。tgf - β 1 mRNA的表达在第3天和第4天达到峰值，ifn - γ mRNA的表达在第3天达到峰值，然后回到背景水平。tnf - α mRNA表达在第2天至第4天最高，IL-8 mRNA水平在第2天至第5天保持升高，在第3天达到峰值，然后回到背景水平。ppd诱导的增殖反应在第3天明显，并在整个研究过程中保持存在。分析结核性胸膜炎中细胞因子的表达可能有助于更好地了解这种结核表现的自愈性质。
Tuberculous pleurisy is a severe inflammatory response induced by Mycobacterium tuberculosis organisms that have escaped from lung granulomata. into the pleural space during pulmonary infection. We have used the guinea pig model of tuberculous pleurisy to examine several aspects of the immune response to this antigen-specific inflammatory event. Pleurisy was induced by injection of heat-killed M. tuberculosis H37Rv directly into the pleural space of guinea pigs previously vaccinated with M. bovis BCG. Four animals were euthanized each day over a period of 9 days. Fluid in the pleural cavity was analyzed for transforming growth factor PI (TGF-beta1) and total interferon (IFN) protein levels. In addition, RNA was obtained from pleural cells and examined for TGF-beta1, tumor necrosis factor alpha (TNF-alpha), IFN-gamma, and interleukin-8 (IL-8) expression by real-time PCR. Finally, pleural cells were examined for the ability to proliferate in response to concanavalin A and purified protein derivative (PPD) in vitro. In the pleural fluid, TGF-beta1 protein concentrations increased over the course of the inflammatory response while IFN protein levels were not significantly altered. Expression of TGF-beta1 mRNA peaked on days 3 and 4, and IFN-gamma mRNA expression peaked on day 3 and then returned to background levels. TNF-alpha mRNA expression was highest on days 2 to 4, and IL-8 mRNA levels remained elevated between days 2 and 5, peaking on day 3 before returning to background levels. PPD-induced proliferative responses were evident by day 3 and remained present throughout the study. Analysis of cytokine expression during tuberculous pleurisy may lead to a better understanding of the self-healing nature of this manifestation of tuberculosis.