Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo - 24/12/11
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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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, exacerbation, picornavirus, rhinovirus, gene expression, gene networks, innate immunity, interferons, systems biology
Abbreviations used : CHUK, FDR, IRF, KEGG, NF-κB, NLR, STAT, TLR, WGCNA, XBP-1
Plan
Supported by National Institutes of Health grant HL080083. A.B. is the recipient of a Medical Research Fellowship from the Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia. |
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Disclosure of potential conflict of interest: F. D. Martinez has consultant arrangements with MedImmune and Bayer. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 1
P. 88-94 - janvier 2012 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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