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Series GSE39304 Query DataSets for GSE39304
Status Public on Feb 27, 2013
Title Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD
Organism Mus musculus
Experiment type Expression profiling by array
Summary Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
 
Overall design Temporal genomic characterization of lung homogenate from male BALB/cJ mice treated intranasally with poly I:C or saline was carried out at 7 timepoints post poly I:C/saline adiministration (2, 6, 24, 48, 72, 96, 168 hours). Mice were anesthetized with isoflurane and intranasally (i.n.) administered saline or poly I:C (InvivoGen, San Diego, CA) at a sub-maximal dose of 30 µg in 50 µl sterile saline. For time course studies, the 30 µg was administered i.n. once and assessed from 2 – 168 hours. Total RNA was isolated from the mouse lung tissue of poly I:C and saline treated mice across 7 time points (2, 6, 24, 48, 72, 96, and 168 hours, n=6 per group) and homogenized in QIAzol reagent. Purified total RNA was amplified and labeled using NuGen Ovation kits (NuGEN Technologies, Inc., San Carlos, CA) and RNA from samples was hybridized to Affymetrix Mouse 430 2.0 arrays.
 
Contributor(s) Sridhar S, Stevenson CS
Citation(s) 22990623
Submission date Jul 12, 2012
Last update date Feb 11, 2019
Contact name Sriram Sridhar
E-mail sridhars@medimmune.com
Phone 6178771485
Organization name MedImmune
Department Translational Medicine
Street address 1 MedImmune Way
City Gaithersburg
State/province MD
ZIP/Postal code 20878
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (84)
GSM960509 lung_Saline_7d_A1
GSM960510 lung_Saline_7d_A2
GSM960511 lung_Saline_7d_A3
Relations
BioProject PRJNA170526

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39304_RAW.tar 330.2 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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