STANDARD_NAME GSE9988_ANTI_TREM1_VS_LOW_LPS_MONOCYTE_DN SYSTEMATIC_NAME M5847 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE9988_ANTI_TREM1_VS_LOW_LPS_MONOCYTE_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in comparison of monocytes treated with anti-TREM1 [GeneID=54210] versus monocytes treated with 1 ng/ml LPS (TLR4 agonist). DESCRIPTION_FULL 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. PMID 18292579 GEOID GSE9988 AUTHORS Dower K,Ellis DK,Saraf K,Jelinsky SA,Lin LL CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE9988_2035_200_DN FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ACSL1,ACVR2A,ADA,ANKRD33B,ANO5,AQP9,ARL5B,ARRB1,AZIN1,BCL2A1,BIRC2,BIRC3,BTG3,C11orf75,C11orf96,C12orf61,C19orf61,C1orf122,C1orf61,C22orf37,C22orf45,CASP5,CCL20,CCL23,CCL4,CCRN4L,CD274,CD83,CDK1,CFLAR,CLCF1,CLEC4E,CLIC4,CSF3,CXCL1,CXCL2,CXCL3,DCUN1D3,DENND4A,DENND5A,DNAJA1,DRAM1,DUSP2,E2F7,EBI3,EHD1,EIF1B,EPB41L3,EPM2AIP1,EZH2,FAM49A,FFAR2,FLJ39739,FNBP1,FRMD7,G0S2,GADD45A,GBP1,GCH1,GIMAP5,GPR132,GPR84,GRAMD1A,GTF3C6,HCAR3,HCG26,HCK,HCP5,HDGF,HIVEP1,HIVEP2,HNRNPC,ICAM1,ICAM4,ID2,IER3,IER5,IFNGR2,IGSF6,IL10,IL12B,IL15RA,IL18,IL1A,IL1B,IL20,IL23A,IL36G,IL6,IL8,IRAK2,IRG1,ITGB8,KCNA3,KCNJ2,KIAA0247,LDLR,LIMK2,LOC100302650,LOC100506229,LOC285628,LOC440934,LOC731424,MAP3K8,MARCKS,MCOLN2,MEIR5,MGC39372,MIR155HG,MLF1IP,MMP7,MSH6,MST4,MTF1,NAB1,NBN,NCOA4,NFE2L2,NFKB1,NFKBIA,NFKBIZ,NLRP3,OASL,OAZ2,PDE4B,PDSS1,PELI1,PFKFB3,PHF15,PIK3AP1,PILRA,PIM2,PIM3,PLA1A,PLAC8,PLEKHF2,PLK3,PMAIP1,PNPLA1,PNRC1,PPP1R15B,PSMA6,PSMD5,PTGS2,PTPRJ,PTTG1IP,PTX3,QKI,RAP2C,RAPGEF2,RCSD1,RHOF,RHOH,RHOU,RIN2,RIPK2,RND1,RNF144B,RNF19B,SAMSN1,SAV1,SCN1B,SDC4,SERPINB8,SESTD1,SGPP2,SIAH2,SLC1A3,SLC2A6,SNX18,SOCS3,SOD2,SPECC1L,STAT5A,STX11,SYNPO2,TAB2,TAGAP,TANK,TAOK3,TBC1D10A,TIFA,TLR7,TMEM54,TNF,TNFAIP2,TNFAIP3,TNFAIP6,TNFAIP8,TNFRSF10B,TNFRSF9,TNIP1,TNIP3,TP53INP1,TRAF1,UGP2,ZBTB10,ZC3H12A,ZC3HAV1,ZFX GENE_SYMBOLS ACSL1,ACVR2A,ADA,ANKRD33B,ANO5,AQP9,ARL5B,ARRB1,AZIN1,BCL2A1,BIRC2,BIRC3,BTG3,SMCO4,C11orf96,LINC01465,SMG9,C1orf122,MIR9-1HG,LINC00528,ADORA2A-AS1,CASP5,CCL20,CCL23,CCL4,NOCT,CD274,CD83,CDK1,CFLAR,CLCF1,CLEC4E,CLIC4,CSF3,CXCL1,CXCL2,CXCL3,DCUN1D3,DENND4A,DENND5A,DNAJA1,DRAM1,DUSP2,E2F7,EBI3,EHD1,EIF1B,EPB41L3,EPM2AIP1,EZH2,CYRIA,FFAR2,LINC01138,FNBP1,FRMD7,G0S2,GADD45A,GBP1,GCH1,GIMAP5,GPR132,GPR84,GRAMD1A,GTF3C6,HCAR3,,HCK,HCP5,HDGF,HIVEP1,HIVEP2,HNRNPC,ICAM1,ICAM4,ID2,IER3,IER5,IFNGR2,IGSF6,IL10,IL12B,IL15RA,IL18,IL1A,IL1B,IL20,IL23A,IL36G,IL6,CXCL8,IRAK2,ACOD1,ITGB8,KCNA3,KCNJ2,SUSD6,LDLR,LIMK2,,LINC01093,MIR3142HG,CT75,MIR3945HG,MAP3K8,MARCKS,MCOLN2,SFR1,SERPINB9P1,MIR155HG,CENPU,MMP7,MSH6,STK26,MTF1,NAB1,NBN,NCOA4,NFE2L2,NFKB1,NFKBIA,NFKBIZ,NLRP3,OASL,OAZ2,PDE4B,PDSS1,PELI1,PFKFB3,JADE2,PIK3AP1,PILRA,PIM2,PIM3,PLA1A,PLAC8,PLEKHF2,PLK3,PMAIP1,PNPLA1,PNRC1,PPP1R15B,PSMA6,PSMD5,PTGS2,PTPRJ,PTTG1IP,PTX3,QKI,RAP2C,RAPGEF2,RCSD1,RHOF,RHOH,RHOU,RIN2,RIPK2,RND1,RNF144B,RNF19B,SAMSN1,SAV1,SCN1B,SDC4,SERPINB8,SESTD1,SGPP2,SIAH2,SLC1A3,SLC2A6,SNX18,SOCS3,SOD2,SPECC1L,STAT5A,STX11,SYNPO2,TAB2,TAGAP,TANK,TAOK3,TBC1D10A,TIFA,TLR7,TMEM54,TNF,TNFAIP2,TNFAIP3,TNFAIP6,TNFAIP8,TNFRSF10B,TNFRSF9,TNIP1,TNIP3,TP53INP1,TRAF1,UGP2,ZBTB10,ZC3H12A,ZC3HAV1,ZFX FOUNDER_NAMES