人肺器官培养模型中对 H3N2 和 H1N1 流感病毒感染的固有免疫反应。
Innate immune response to H3N2 and H1N1 influenza virus infection in a human lung organ culture model.
机构信息
Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, RM 425, RP1, 800 N. Research Pkwy., Oklahoma City, OK 73104, USA.
出版信息
Virology. 2010 Jan 20;396(2):178-88. doi: 10.1016/j.virol.2009.10.016. Epub 2009 Nov 12.
Abstract
We studied cytokine responses to influenza virus PR8 (H1N1) and Oklahoma/309/06 (OK/06, H3N2) in a novel human lung tissue model. Exposure of the model to influenza virus rapidly activated the mitogen-activated protein kinase signaling (MAPK) pathways ERK, p38 and JNK. In addition, RNase protection assay demonstrated the induction of several cytokine and chemokine mRNAs by virus. This finding was reflected at the translational level as IL-6, MCP-1, MIP-1 alpha/beta, IL-8 and IP-10 proteins were induced as determined by ELISA. Immunohistochemistry for IP-10 and MIP-1 alpha revealed that alveolar epithelial cells and macrophages were the source of these two cytokines. Taken together, both PR8 and OK/06 cause similar induction of cytokines in human lung, although OK/06 is less effective at inducing the chemokines MCP-1 and IL-8. This human organ culture model should thus provide a relevant platform to study the biological responses of human lung to influenza virus infection.
摘要
我们在一种新型的人肺组织模型中研究了流感病毒 PR8（H1N1）和俄克拉荷马/309/06（OK/06，H3N2）引起的细胞因子反应。该模型接触流感病毒后，迅速激活了丝裂原活化蛋白激酶信号转导（MAPK）途径 ERK、p38 和 JNK。此外，核糖核酸酶保护分析表明，病毒诱导了几种细胞因子和趋化因子 mRNA 的表达。这一发现反映在翻译水平上，因为 ELISA 测定表明 IL-6、MCP-1、MIP-1 alpha/beta、IL-8 和 IP-10 蛋白被诱导。免疫组织化学分析 IP-10 和 MIP-1 alpha 表明，肺泡上皮细胞和巨噬细胞是这两种细胞因子的来源。总之，PR8 和 OK/06 都会引起人肺中类似的细胞因子诱导，尽管 OK/06 在诱导趋化因子 MCP-1 和 IL-8 方面的效果较差。因此，这种人器官培养模型应该为研究流感病毒感染对人肺的生物学反应提供一个相关的平台。
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