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| Status |
Public on Mar 20, 2008 |
| Title |
Innate immune repsonses to TREM-1 activation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
TREM-1 is an orphan immunoreceptor expressed on monocytes, macrophages, and neutrophils. TREM-1 associates with and signals via the adapter protein DAP12/TYROBP, which contains an immunoreceptor tyrosine-based activation motif (ITAM). TREM-1 activation by receptor cross-linking is pro-inflammatory, and can amplify cellular responses to Toll-like receptor (TLR) ligands such as bacterial lipopolysaccharide (LPS). To investigate the cellular consequences of TREM-1 activation, we have characterized global gene expression changes in human monocytes in response to TREM-1 cross-linking in comparison to and combined with LPS. Both TREM-1 activation and LPS up-regulate chemokines, cytokines, matrix metalloproteases, and PTGS/COX2, consistent with a core inflammatory response. However, other immunomodulatory factors are selectively induced, including SPP1 and CSF1 (i.e., M-CSF) by TREM-1 activation and IL-23 and CSF3 (i.e., G-CSF) by LPS. Additionally, cross-talk between TREM-1 activation and LPS occurs on multiple levels. While synergy in GM-CSF protein production is reflected in commensurate mRNA abundance, comparable synergy in IL-1b protein production is not. TREM-1 activation also attenuates the induction of some LPS target genes, including those that encode IL-12 cytokine family subunits. Whereas positive TREM-1 outputs are abolished by the PI3K inhibitor wortmannin, this attenuation is largely PI3K-independent. These experiments provide a detailed analysis of the cellular consequences of TREM-1 activation, and highlight some of the complexity in signal integration between ITAM- and TLR-mediated signaling.
Keywords: Stress response
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| Overall design |
11 anonymous donors were treated with Vehicle, isotype control antibody, TREM1 antibody, LPS, isotype control antibody plus LPS and TREM1 antibody plus LPS
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| Contributor(s) |
Jelinsky SA, Dower K |
| Citation(s) |
18292579 |
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| Submission date |
Dec 20, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Scott Jelinsky |
| E-mail(s) |
Scott.Jelinsky@pfizer.com
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| Phone |
617-674-7272
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| Organization name |
Pfizer
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| Department |
Inflammation and Immunology
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| Lab |
Computational Precision Medicine
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| Street address |
610 Main Street
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (62)
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| Relations |
| BioProject |
PRJNA104009 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9988_RAW.tar |
465.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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