期刊
LIFE SCIENCES
卷 74, 期 20, 页码 2563-2576出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2003.10.010
关键词
dsRNA; poly[rI center dot rC]; interferon-gamma; cytokine; lung; acute phase response
资金
- NICHD NIH HHS [HD 36520] Funding Source: Medline
- NINDS NIH HHS [NS 25378] Funding Source: Medline
Double-stranded (ds)RNA is made as a by-product of viral replication. Synthetic dsRNA induces virtually all of the same systemic symptoms as acute viral infections, such as fever and malaise. In order to develop a model of respiratory viral infections (such as influenza) suitable for use in gene knockout mice (where the deleted gene may affect viral replication), we examined C57BL/6 mouse body temperature and locomotor activity responses to the synthetic dsRNA polyriboinosinic . polyribocytidylic acid (poly[rI . rC]) introduced via the intratracheal (IT) route. We compared the IT poly[rI . rC] responses to the well-characterized intraperitoneal (IP) poly[rI . rC] responses. IT poly[rI - rC] failed to induce an acute phase response (APR) in mice, in contrast to IP poly[rI . rC]. However, addition of interferon (IFN)gamma to the IT poly[rI . rC] inoculum induced sustained hypothermia and suppressed locomotor activity responses with similar kinetics to those responses seen in acute mouse influenza. We further examined cytokine, antiviral, muscarinic M-2 receptor and inducible nitric oxide synthase gene expression at 5 hr in the lungs of IT challenged mice. These studies suggested that priming the lung with IFNgamma could enhance proinflammatory (IL1beta, IL6, TNFalpha) cytokine gene expression and suppress interferon gene expression compared to IT poly[rI . rC] alone. No differences were detected for the other genes examined. While further molecular characterization of the model is required, we demonstrate that IT challenge with combined poly[rI - rC] and IFNgamma closely simulates the APR to an acute respiratory virus, and may serve as a suitable model for analyzing the molecular basis of the viral APR in gene knockout mice. (C) 2004 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据