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J Allergy Clin Immunol. 2012 Jan;129(1):88-94. doi: 10.1016/j.jaci.2011.10.038. Epub 2011 Nov 23.

Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo.

Author information

1
Arizona Respiratory Center, University of Arizona, Tucson, Ariz, USA. anthonyb@ichr.uwa.edu.au

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.

PMID:
22112518
PMCID:
PMC3246116
DOI:
10.1016/j.jaci.2011.10.038
[Indexed for MEDLINE]
Free PMC Article
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