PT - JOURNAL ARTICLE AU - Sriram Sridhar AU - Paul Harris AU - John Allard AU - Ruoqi Peng AU - Palani Ravindran AU - Hans Bitter AU - Michael E. Burczynski AU - Jay S. Fine AU - Christopher S. Stevenson TI - Temporal characterization of murine genomic response to poly I:C stimulation reveals tri-phasic inflammatory response signatures DP - 2011 Sep 01 TA - European Respiratory Journal PG - p815 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p815.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p815.full SO - Eur Respir J2011 Sep 01; 38 AB - Introduction: Poly I:C mimics a viral infection through the activation TLR3 and RNA helicases. Our aim was to characterize molecular changes occurring in the lung after polyI:C exposure in mice.Methods: BALB/c mice were administered saline or poly I:C (30 μg/animal). At 7 timepoints after dosing (2-168h), poly I:C- and saline-treated mice were sacrificed, bronchoalveolar lavage was performed and lungs were snap-frozen. RNA from lung homogenates was isolated using the NuGen labeling method and assessed on Affymetrix standard murine whole genome arrays (MOE430 2.0) (n=6 per group). Differentially expressed genes were determined using an ANOVA, with pairwise comparisons between poly I:C and saline treatment at each timepoint. Functional ontologies were determined using GO annotations. Gene set enrichment analysis (GSEA) was determined for cytokine and immune cell signatures compiled from the literature.Results: The peak response occurred 6-48h post-treatment. Hierarchical clustering across the study revealed 3 distinct temporal clusters (early, mid, and late phase). Inflammatory processes were enriched in the early phase (2-6h), TLR/IL-1 signaling genes in the mid phase (6-48h), and cell cycle pathways in the late phase (>72h). GSEA revealed activated NK and dendritic cell signatures up to 96h post-challenge, while several immune and myeloid related gene modules were also up-regulated between 6-96h post-challenge.Conclusions: Inflammatory signatures including TLR and IL1-related genes were highly up-regulated in response to poly I:C challenge, indicating a strong inflammatory response potentially driven by NK and dendritic cells in the lungs of mice.