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| Status |
Public on Jun 25, 2008 |
| Title |
response to LPS of WT and IRAK4 kinase dead mouse bone marrow macrophages |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
Keywords: genetic modification, strain comparison, cell stimulation, time course, anti-bacterial response, innate immune response, inflammatory response
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| 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.
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| Contributor(s) |
Koziczak-Holbro M, Gram H, Kinzel B, Glueck A, Hartmann N, Letzkus M |
| Citation(s) |
18266302 |
| Submission date |
Sep 13, 2007 |
| Last update date |
Aug 02, 2019 |
| Contact name |
Anton Glück |
| E-mail(s) |
anton.glueck@novartis.com
|
| Organization name |
Novartis Institutes for BioMedical Research
|
| Street address |
WSJ-386.13.50
|
| City |
Basel |
| ZIP/Postal code |
4002 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
|
| GSM229589 |
WT_BoneMarrowMacrophages_unstimulated_4hours_rep1 |
| GSM229590 |
WT_BoneMarrowMacrophages_unstimulated_4hours_rep2 |
| GSM229591 |
WT_BoneMarrowMacrophages_LPS-stimulated_1hour_rep1 |
| GSM229592 |
WT_BoneMarrowMacrophages_LPS-stimulated_1hour_rep2 |
| GSM229593 |
WT_BoneMarrowMacrophages_LPS-stimulated_4hours_rep1 |
| GSM229594 |
WT_BoneMarrowMacrophages_LPS-stimulated_4hours_rep2 |
| GSM229595 |
IRAK4-KD_BoneMarrowMacrophages_unstimulated_4hours_rep1 |
| GSM229596 |
IRAK4-KD_BoneMarrowMacrophages_unstimulated_4hours_rep2 |
| GSM229597 |
IRAK4-KD_BoneMarrowMacrophages_LPS-stimulated_1hour_rep1 |
| GSM229598 |
IRAK4-KD_BoneMarrowMacrophages_LPS-stimulated_1hour_rep2 |
| GSM229599 |
IRAK4-KD_BoneMarrowMacrophages_LPS-stimulated_4hours_rep1 |
| GSM229600 |
IRAK4-KD_BoneMarrowMacrophages_LPS-stimulated_4hours_rep2 |
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| Relations |
| BioProject |
PRJNA102541 |
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