ArrayExpress Uploader07769IL-1betaIRAK-4 deficient1IL-1betaIRAK-4 deficient1IL-1betaIRAK-4 deficient4IL-1betaIRAK-4 deficient4noneIRAK-4 deficient4noneIRAK-4 deficient4nonewild_type4IL-1betawild_type1IL-1betawild_type1IL-1betawild_type4IL-1betawild_type4nonewild_type4arrayexpress_sid6IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as...17337443E-GEOD-6789/profile/8773/arrayexpressuploader312proteinDec.12, 2014Falsetranscription-profiling-of-mouse-embryonic-fibro-5E-GEOD-6789_A-AFFY-45Transcription profiling of mouse embryonic fibroblasts from wild type and IRAK-4 kinase dead animals stimulated with IL-1b for different durations to identify IRAK-4 kinase-dependent IL-1b response genes.Nov.13, 2014IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, knock-in mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice with a number of experimental techniques demonstrated that they greatly lack responsiveness to stimulation with IL-1b or a Toll-like receptor 7 (TLR7) agonist. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent IL-1b response genes in mouse embryonic fibroblasts and revealed that the induction of IL-1b-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R/TLR7-mediated induction of inflammatory responses. Experiment Overall Design: The response of mouse embryonic fibroblasts from WT and IRAK4 kinase dead animals to stimulation with IL-1b at two time points was determined. There were 12 samples in total, 6 from WT and 6 from IRAK4 kinase dead cells; for each strain there were 3 conditions: growth for 4 hours without stimulation (the strain-specific control), growth for 1 hour with stimulation, and growth for 4 hours with stimulation; for each condition there were two biological replicates.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-6789mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-6789/samples/