STANDARD_NAME GSE9988_LPS_VS_LPS_AND_ANTI_TREM1_MONOCYTE_DN SYSTEMATIC_NAME M5857 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE9988_LPS_VS_LPS_AND_ANTI_TREM1_MONOCYTE_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in comparison of monocytes treated with 5000 ng/ml LPS (TLR4 agonist) versus monocytes treated with anti-TREM1 [GeneID=54210]. 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_2040_200_DN FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ACOX3,ACRC,ACSL3,ACVR1,ADCK2,ADCY3,AGAP3,AKIRIN2,ANKRD10,ANKRD28,ANKRD57,ANKS6,ASPH,ATF3,ATP6V1B2,ATP6V1D,ATP6V1H,BAG3,BANP,BCAR3,BHLHE40,BRI3,C14orf109,C14orf169,C17orf79,C17orf91,C20orf20,C6orf114,C9orf47,CALU,CAMSAP1,CAMTA2,CCR1,CD68,CD84,CDC42EP3,CEBPB,CKS2,CNST,COL15A1,CORO1C,CRTAM,CRY1,CSF1,CSTB,CTSL1,DAB2,DCUN1D4,DDIT3,DPH5,DTL,DYRK3,EDN1,EIF2AK3,FAM131A,FAM83G,FBXL5,FKBP15,FLJ43663,FNIP2,FOSL1,GEM,GLA,GNA13,GNPDA1,GPCPD1,GTF2A1,HAVCR2,HES4,IL36RN,ITGAX,ITPR1,KCTD7,KIAA1704,KLHL21,KLHL6,LBH,LHFPL2,LOC100132987,LOC100287039,LOC100287719,LOC100288781,LOC151534,LOC221710,LOC283050,LOC284454,LOC401588,LOC646329,LONP1,LONRF3,LPL,LRFN4,LRRC33,LY9,MAFK,MAP4K3,MAPK13,MESDC1,MFI2,MIR21,MMP1,MMP10,MMP19,MOAP1,MOBKL1A,NAA50,NEDD4L,NEU1,NHEDC2,NPC1,NR4A2,NRARP,NRBP1,NRIP3,NUDT4,OGT,OLIG2,PHF13,PISD,PLCXD1,PLEKHM1,PLEKHM2,PLEKHO1,PPAP2B,PPARG,PPFIA1,PRKAG2,PTPRE,RABGEF1,RB1CC1,RGS1,RHEB,RHOB,RHOBTB3,RLF,RNASEK,RNF19A,RRAD,RRAGC,RRAGD,RRN3P3,S1PR3,SCARB2,SCG5,SDSL,SERPINE1,SERTAD2,SGK1,SH3BP5,SH3D21,SIGLEC15,SLC19A2,SLC3A2,SLCO4A1,SNAPC1,SNUPN,SNX33,SNX9,SOS1,SPAG5,SPINK1,SPP1,SPRY2,ST18,ST3GAL6,STARD8,STX3,STX4,SYN2,TBC1D2,TBC1D7,TCEAL3,TCTEX1D2,TDRD9,TEX10,THAP4,TLR5,TM7SF4,TMEM181,TMEM38B,TMEM55B,TMEM65,TNFRSF12A,TNFSF14,TNFSF15,TPCN2,TRIB1,TSC22D1,TXN,UBR7,UPP1,VMP1,VPS37B,WBP5,ZBTB2,ZBTB43,ZC3HC1,ZCCHC6,ZNF295,ZSCAN5A GENE_SYMBOLS ACOX3,GCNA,ACSL3,ACVR1,ADCK2,ADCY3,AGAP3,AKIRIN2,ANKRD10,ANKRD28,SOWAHC,ANKS6,ASPH,ATF3,ATP6V1B2,ATP6V1D,ATP6V1H,BAG3,BANP,BCAR3,BHLHE40,BRI3,LYSET,RIOX1,COPRS,MIR22HG,MRGBP,GFOD1,S1PR3,CALU,CAMSAP1,CAMTA2,CCR1,CD68,CD84,CDC42EP3,CEBPB,CKS2,CNST,COL15A1,CORO1C,CRTAM,CRY1,CSF1,CSTB,CTSL,DAB2,DCUN1D4,DDIT3,DPH5,DTL,DYRK3,EDN1,EIF2AK3,FAM131A,FAM83G,FBXL5,FKBP15,LINC-PINT,FNIP2,FOSL1,GEM,GLA,GNA13,GNPDA1,GPCPD1,GTF2A1,HAVCR2,HES4,IL36RN,ITGAX,ITPR1,KCTD7,GPALPP1,KLHL21,KLHL6,LBH,LHFPL2,LINC00595,,,,LBX2-AS1,SMIM13,ZMIZ1-AS1,MIR23AHG,ZNF674-AS1,LINC-PINT,LONP1,LONRF3,LPL,LRFN4,NRROS,LY9,MAFK,MAP4K3,MAPK13,TLNRD1,MELTF,MIR21,MMP1,MMP10,MMP19,MOAP1,MOB1B,NAA50,NEDD4L,NEU1,SLC9B2,NPC1,NR4A2,NRARP,NRBP1,NRIP3,NUDT4,OGT,OLIG2,PHF13,PISD,PLCXD1,PLEKHM1,PLEKHM2,PLEKHO1,PLPP3,PPARG,PPFIA1,PRKAG2,PTPRE,RABGEF1,RB1CC1,RGS1,RHEB,RHOB,RHOBTB3,RLF,RNASEK,RNF19A,RRAD,RRAGC,RRAGD,RRN3P3,S1PR3,SCARB2,SCG5,SDSL,SERPINE1,SERTAD2,SGK1,SH3BP5,SH3D21,SIGLEC15,SLC19A2,SLC3A2,SLCO4A1,SNAPC1,SNUPN,SNX33,SNX9,SOS1,SPAG5,SPINK1,SPP1,SPRY2,ST18,ST3GAL6,STARD8,STX3,STX4,SYN2,TBC1D2,TBC1D7,TCEAL3,DYNLT2B,TDRD9,TEX10,THAP4,TLR5,DCSTAMP,TMEM181,TMEM38B,PIP4P1,TMEM65,TNFRSF12A,TNFSF14,TNFSF15,TPCN2,TRIB1,TSC22D1,TXN,UBR7,UPP1,VMP1,VPS37B,TCEAL9,ZBTB2,ZBTB43,ZC3HC1,TUT7,ZBTB21,ZSCAN5A FOUNDER_NAMES