ArrayExpress Uploader07925arrayexpress_sid6IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as...18266302E-GEOD-9037/profile/8773/arrayexpressuploader012bonebone marrowproteinDec.12, 2014Falsetranscription-profiling-of-mouse-bone-marrow-macroE-GEOD-9037_A-AFFY-45Transcription profiling of mouse bone marrow macrophages from WT and IRAK4 kinaseNov.18, 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 bone marrow macrophages obtained from WT and IRAK-4 KD mice with a number of experimental techniques demonstrated that the IRAK-4 KD cells greatly lack responsiveness to stimulation with the Toll-like receptor 4 (TLR4) agonist LPS. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent LPS response genes and revealed that the induction of LPS-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 TLR4-mediated induction of inflammatory responses. Experiment Overall Design: The response of mouse bone marrow macrophages from WT and IRAK4 kinase dead animals to stimulation with LPS 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-9037mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-9037/samples/