Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide.

Dower, K., Ellis, D.K., Saraf, K, Jelinsky, S.A., Lin, L.L.
Journal   J Immunol Methods
Species  
Analytes Measured   GM-CSF , IL-12 IL-23p40
Matrix Tested   Cell culture supernatants
Year   2008
Volume   180
Page Numbers   3520-34
Application   Cytokines and Chemokines
Abstract
TREM-1 (triggering receptor expressed on myeloid cells-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 ITAM. TREM-1 activation by receptor cross-linking has been shown to be proinflammatory and to amplify some cellular responses to TLR ligands such as bacterial 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. Although synergy in GM-CSF protein production is reflected in commensurate mRNA abundance, comparable synergy in IL-1beta 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. Where tested, positive TREM-1 outputs are greatly reduced by the PI3K inhibitor wortmannin, whereas this attenuation is largely PI3K independent. These experiments provide a detailed analysis of the cellular consequences of TREM-1 activation and highlight the complexity in signal integration between ITAM- and TLR-mediated signaling.

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Multiplex
U-PLEX Immuno-Oncology Group 1 (human) Assays
APRIL/TNFSF13, BAFF-R/TNFRSF13C, BCMA/TNFRSF17, CD20, CD27, CD28, CD40L (soluble), CD276/B7-H3, CTACK, CTLA-4, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, E-Selectin, FGF (basic), FLT3L, Fractalkine, Galectin-9, G-CSF, GITR/TNFRSF18, GITRL/TNFSF18, GM-CSF, gp130 (soluble), Granzyme A, Granzyme B, GRO-α, HAVCR2/TIM-3, HVEM/TNFRSF14, I-309, ICOS, ICOS-L/B7-H2, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, LAG3, LIGHT/TNFSF14, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIG, MIP-1α, MIP-1β, MIP-5, MMP-1, MMP-2, MMP-7, MMP-9 (total), Nectin-4, OX40/TNFRSF4, PD1 (epitope 1), PD1 (epitope 2), PD-L1 (epitope 1), PD-L1 (epitope 2), PD-L2, Pentraxin 3, Perforin, PlGF, proMMP-9, P-Selectin, RAGE (soluble), RANKL/TNFSF11, RANTES, S100A12, Tie-2, TIGIT, TLR1, TNF-α, TNF-β, TNF-RI, TNF-RII, TPO, TRAIL, TSLP, VEGF-A, VEGF-D, VEGFR-1/Flt-1, YKL-40 | Human
Multiplex
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