Human Gene Set: GSE9037_WT_VS_IRAK4_KO_LPS_1H_STIM_BMDM_DN


Standard name GSE9037_WT_VS_IRAK4_KO_LPS_1H_STIM_BMDM_DN
Systematic name M5816
Brief description Genes down-regulated in comparison of untreated wild type macrophages at 1 h versus those from IRAK4 [GeneID=51135] deficient mice treated with LPS (TLR4 agonist) at 1 h.
Full description or abstract IRAK-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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 18266302   Authors: Koziczak-Holbro M,Glück A,Tschopp C,Mathison JC,Gram H
Exact source GSE9037_1748_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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