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| Status |
Public on Mar 30, 2007 |
| Title |
response to IL-1b of WT and IRAK4 kinase dead mouse embryonic fibroblasts |
| 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 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.
Keywords: genetic modification, strain comparison, cell stimulation, time course, inflammatory response
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| 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.
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| Contributor(s) |
Koziczak-Holbro M, Gram H, Kinzel B, Glueck A, Hartmann N, Letzkus M |
| Citation(s) |
17337443 |
| |
| Submission date |
Jan 18, 2007 |
| Last update date |
Feb 11, 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 |
|
| Samples (12)
|
| GSM156797 |
WT-MEFs_IL1b-stimulated_1hour_rep2 |
| GSM156798 |
WT-MEFs_IL1b-stimulated_4hours_rep1 |
| GSM156799 |
WT-MEFs_IL1b-stimulated_4hours_rep2 |
| GSM156800 |
IRAK4-KD-MEFs_unstimulated_4hours_rep1 |
| GSM156801 |
IRAK4-KD-MEFs_unstimulated_4hours_rep2 |
| GSM156802 |
IRAK4-KD-MEFs_IL1b-stimulated_1hour_rep1 |
| GSM156803 |
IRAK4-KD-MEFs_IL1b-stimulated_1hour_rep2 |
| GSM156804 |
IRAK4-KD-MEFs_IL1b-stimulated_4hours_rep1 |
| GSM156805 |
IRAK4-KD-MEFs_IL1b-stimulated_4hours_rep2 |
|
| Relations |
| BioProject |
PRJNA99223 |
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