在体病毒诱导的哮喘急性发作中，干扰素调节因子7是干扰素介导反应的中心
2012/01/31
摘要
背景：对于哮喘儿童，哮喘急性发作是哮喘发病和卫生保健的沉重负担。大多数哮喘急性发作由病毒感染所导致，然而，其潜在的机制尚未系统性研究。
目的：本研究旨在哮喘患儿中阐明病毒诱导的哮喘急性发作的分子网络。
方法：对有急性发作倾向的哮喘患儿进行前瞻性随访。在小核糖核酸病毒诱导的中度哮喘急性发作急性期及7～14天后，检测鼻腔灌洗液的基因表达水平。采用共表达网络分析和之前的了解来重建基因网络。
结果：研究结果显示，与哮喘急性发作7～14天相比，由1000个以上基因组成的复杂模块化程序在急性急性发作期上调。模块富含连贯的细胞过程，包括干扰素诱导的抗病毒反应、固有病原体感应、伤口反应、小核仁RNA和泛素-蛋白酶体及溶酶体降解旁路。模块接线图的重建显示，存在超级连接枢纽节点，大部分为干扰素调节因子7，该因子被认为是连接干扰素介导的抗病毒反应的主要中心。
结论：本研究为验证网络提供了整合的观点，体内该网络在病毒诱导的哮喘急性发作时存在上调。我们发现，一系列的固有信号中心，可以作为哮喘治疗新的靶点。
（陈欣 审校）
J Allergy Clin Immunol. 2011 Nov 22. [Epub ahead of print]
Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo.
Bosco A, Ehteshami S, Panyala S, Martinez FD.
Source
Arizona Respiratory Center, University of Arizona, Tucson, Ariz; Telethon Institute for Child Health Research and the Centre for Child Health Research, the University of Western Australia, Perth, Australia.
Abstract
BACKGROUND: Exacerbations are responsible for a substantial burden of morbidity and health care use in children with asthma. Most asthma exacerbations are triggered by viral infections; however, the underlying mechanisms have not been systematically investigated.
OBJECTIVE: The objective of this study was to elucidate the molecular networks that underpin virus-induced exacerbations in asthmatic children in vivo.
METHODS: We followed exacerbation-prone asthmatic children prospectively and profiled global patterns of gene expression in nasal lavage samples obtained during an acute, moderate, picornavirus-induced exacerbation and 7 to 14 days later. Coexpression network analysis and prior knowledge was used to reconstruct the underlying gene networks.
RESULTS: The data showed that an intricate modular program consisting of more than 1000 genes was upregulated during acute exacerbations in comparison with 7 to 14 days later. The modules were enriched for coherent cellular processes, including interferon-induced antiviral responses, innate pathogen sensing, response to wounding, small nucleolar RNAs, and the ubiquitin-proteosome and lysosome degradation pathways. Reconstruction of the wiring diagram of the modules revealed the presence of hyperconnected hub nodes, most notably interferon regulatory factor 7, which was identified as a major hub linking interferon-mediated antiviral responses.
CONCLUSIONS: This study provides an integrated view of the inflammatory networks that are upregulated during virus-induced asthma exacerbations in vivo. A series of innate signaling hubs were identified that could be novel therapeutic targets for asthma attacks.
J Allergy Clin Immunol. 2011 Nov 22. [Epub ahead of print]
背景：对于哮喘儿童，哮喘急性发作是哮喘发病和卫生保健的沉重负担。大多数哮喘急性发作由病毒感染所导致，然而，其潜在的机制尚未系统性研究。
目的：本研究旨在哮喘患儿中阐明病毒诱导的哮喘急性发作的分子网络。
方法：对有急性发作倾向的哮喘患儿进行前瞻性随访。在小核糖核酸病毒诱导的中度哮喘急性发作急性期及7～14天后，检测鼻腔灌洗液的基因表达水平。采用共表达网络分析和之前的了解来重建基因网络。
结果：研究结果显示，与哮喘急性发作7～14天相比，由1000个以上基因组成的复杂模块化程序在急性急性发作期上调。模块富含连贯的细胞过程，包括干扰素诱导的抗病毒反应、固有病原体感应、伤口反应、小核仁RNA和泛素-蛋白酶体及溶酶体降解旁路。模块接线图的重建显示，存在超级连接枢纽节点，大部分为干扰素调节因子7，该因子被认为是连接干扰素介导的抗病毒反应的主要中心。
结论：本研究为验证网络提供了整合的观点，体内该网络在病毒诱导的哮喘急性发作时存在上调。我们发现，一系列的固有信号中心，可以作为哮喘治疗新的靶点。
（陈欣 审校）
J Allergy Clin Immunol. 2011 Nov 22. [Epub ahead of print]
Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo.
Bosco A, Ehteshami S, Panyala S, Martinez FD.
Source
Arizona Respiratory Center, University of Arizona, Tucson, Ariz; Telethon Institute for Child Health Research and the Centre for Child Health Research, the University of Western Australia, Perth, Australia.
Abstract
BACKGROUND: Exacerbations are responsible for a substantial burden of morbidity and health care use in children with asthma. Most asthma exacerbations are triggered by viral infections; however, the underlying mechanisms have not been systematically investigated.
OBJECTIVE: The objective of this study was to elucidate the molecular networks that underpin virus-induced exacerbations in asthmatic children in vivo.
METHODS: We followed exacerbation-prone asthmatic children prospectively and profiled global patterns of gene expression in nasal lavage samples obtained during an acute, moderate, picornavirus-induced exacerbation and 7 to 14 days later. Coexpression network analysis and prior knowledge was used to reconstruct the underlying gene networks.
RESULTS: The data showed that an intricate modular program consisting of more than 1000 genes was upregulated during acute exacerbations in comparison with 7 to 14 days later. The modules were enriched for coherent cellular processes, including interferon-induced antiviral responses, innate pathogen sensing, response to wounding, small nucleolar RNAs, and the ubiquitin-proteosome and lysosome degradation pathways. Reconstruction of the wiring diagram of the modules revealed the presence of hyperconnected hub nodes, most notably interferon regulatory factor 7, which was identified as a major hub linking interferon-mediated antiviral responses.
CONCLUSIONS: This study provides an integrated view of the inflammatory networks that are upregulated during virus-induced asthma exacerbations in vivo. A series of innate signaling hubs were identified that could be novel therapeutic targets for asthma attacks.
J Allergy Clin Immunol. 2011 Nov 22. [Epub ahead of print]
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