 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 12, 2014 |
| Title |
Genome-wide expression analysis demonstrates a dominant role of TLR4 for activation of human phagocytes by the alarmin MRP8 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The alarmins myeloid-related protein (MRP) 8 and MRP14 are the dominant cytoplasmic proteins in phagocytes. After release by activated phagocytes extracellular MRP8/MRP14 complexes promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis or inflammatory bowel disease. As receptors for the pro-inflammatory effects of human MRP8, the active component of the MRP8/MRP14-complex, Toll-like receptor (TLR) 4 and the multi-ligand receptor of advanced glycation end products (RAGE) are controversial discussed. Using a comparative bioinformatics analysis between genome-wide response patterns of monocytes to MRP8, endotoxin and different cytokines we demonstrated a dominant role of TLR4 during MRP8-mediated phagocyte activation. The relevance of this signaling pathway could be confirmed in independent cell models for TLR4 and RAGE dependent signaling in mouse and man. In addition to well-known proinflammatory functions of MRP8 our systems biology approach unraveled a novel anti-apoptotic effect of MRP8 on monocytes which was confirmed in independent functional experiments. Our data define the dominance of the TLR4-MRP8 axis in activation of human phagocytes which represents a novel attractive target for modulation of overwhelming innate immune responses.
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
|
| |
|
| Overall design |
Human blood monocyte stimulated with various stimuli (control, MRP8, LPS, TNF, IL1) were selected for RNA extraction and hybridization on Affymetrix microarrays.
|
| |
|
| Contributor(s) |
Fassl SK, Austermann J, Papantonopoulou O, Riemenschneider M, Xue J, Spiekermann C, Witten A, Viemann D, Stoll M, Schultze JL, Roth J, Vogl T |
| Citation(s) |
25505274 |
| |
| Submission date |
Apr 10, 2014 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
[email protected]
|
| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
|
| Department |
Genomics and Immunoregulation
|
| Street address |
Carl-Troll-Strasse 31
|
| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
| |
|
| Platforms (2) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (19)
|
|
| Relations |
| BioProject |
PRJNA244307 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56681_RAW.tar |
81.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...