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Series GSE9988 Query DataSets for GSE9988
Status Public on Mar 20, 2008
Title Innate immune repsonses to TREM-1 activation
Organism Homo sapiens
Experiment type Expression profiling by array
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
 
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
 
Contributor(s) Jelinsky SA, Dower K
Citation(s) 18292579
Submission date Dec 20, 2007
Last update date Jan 08, 2019
Contact name Scott Jelinsky
E-mail Scott.Jelinsky@pfizer.com
Phone 617-674-7272
Organization name Pfizer
Department Inflammation and Immunology
Lab Computational Precision Medicine
Street address 610 Main Street
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (62)
GSM252423 Anti-Trem1 2 hrs Donor 1
GSM252424 Anti-Trem1 2 hrs Donor 3
GSM252425 Anti-Trem1 2 hrs Donor 11
Relations
BioProject PRJNA104009

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE9988_RAW.tar 465.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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