STANDARD_NAME GSE9988_LPS_VS_LOW_LPS_MONOCYTE_UP SYSTEMATIC_NAME M5854 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE9988_LPS_VS_LOW_LPS_MONOCYTE_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in comparison of monocytes treated with 5000 ng/ml LPS (TLR4 agonist) versus those 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_2039_200_UP FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS A2M,ABCA9,ADAM20,AMPH,ANKRD26P3,ANKRD29,AP1S3,ARHGAP20,B3GALT2,BICC1,BMX,BNIP1,C12orf75,C14orf167,C18orf2,C1orf145,C1orf187,C20orf103,C21orf34,C4BPB,C4orf26,C5orf42,C5orf56,C6orf10,CABP2,CABS1,CABYR,CD28,CDCA8,CFHR4,CGN,CHRM4,CLDN20,CMTM4,CNKSR2,CPO,CTLA4,CYP4A11,DEPTOR,DIAPH3,DOPEY2,DPEP3,DRD2,E2F8,EDA2R,EIF2B2,ELMOD1,EPYC,ERCC6L,FAM194A,FAM19A5,FAM27D1,FANCI,FBXL12,FBXO16,FKBP4,FLJ38379,FLJ38717,FLJ44054,GABRB2,GBP6,GLDC,GNRHR2,GOLGA1,GPR123,GPR19,GREB1L,GSTM5,GTF2H2,GULP1,HERC2P1,HIRIP3,HLA-DPB2,HMGB3P22,HOXA11,HTR3C,IGSF11,JUB,KCNA4,KCND3,KCNJ6,KIAA0748,KIF18A,KLHL3,KRT72,KRTAP19-3,KRTAP2-4,KRTAP4-6,LARP6,LOC100129427,LOC100132147,LOC100132460,LOC100291367,LOC100293830,LOC100505483,LOC100505967,LOC100506451,LOC255480,LOC283033,LOC283501,LOC283731,LOC285696,LOC399875,LOC554207,LOC642924,LOC646576,LOC654841,LOC728716,LRRC31,MAGEH1,ME1,MED22,MGC4859,MPP6,MT1E,MTERF,MTFP1,MUM1,MYL5,MYOC,NCAM2,NCRNA00284,NPY2R,NSAP11,NXPH2,OLIG2,OR10C1,OR10D3,OR1J4,OR7A5,PARG,PBX1,PCA3,PCDHGB6,PCDHGB8P,PHAX,PKLR,PKP3,PLCXD3,PLK4,POU3F2,PRICKLE2,PTHLH,PTPN5,RAD21L1,RAG1,RIC3,RIPPLY1,RPAP3,RUSC1-AS1,SCAND2,SCNN1B,SDHAP1,SEMA4F,SERPINB13,SLC1A7,SLC25A1,SLC38A4,SLC4A10,SLCO2A1,SPRR4,SPRYD3,STATH,STON1,STRBP,STYK1,SYNC,T,TACC2,TATDN3,THRA,TLR5,TMEM225,TMEM72,TRAF3IP2-AS1,TRAP1,TRMT61B,TSPAN5,TTC22,TTTY5,TUBB4,UPK1A,VTCN1,WBP2NL,WDR63,WDR78,WNT2,YAP1,ZACN,ZBTB24,ZNF138,ZNF204P,ZNF208,ZNF28,ZNF320,ZNF354C,ZNF485,ZNF544,ZNF624,ZNF789 GENE_SYMBOLS A2M,ABCA9,ADAM20,AMPH,ANKRD26P3,ANKRD29,AP1S3,ARHGAP20,B3GALT2,BICC1,BMX,BNIP1,C12orf75,DHRS4-AS1,LINC00470,OBSCN-AS1,DRAXIN,LAMP5,MIR99AHG,C4BPB,ODAPH,CPLANE1,IRF1-AS1,TSBP1,CABP2,CABS1,CABYR,CD28,CDCA8,CFHR4,CGN,CHRM4,CLDN20,CMTM4,CNKSR2,CPO,CTLA4,CYP4A11,DEPTOR,DIAPH3,DOP1B,DPEP3,DRD2,E2F8,EDA2R,EIF2B2,ELMOD1,EPYC,ERCC6L,ERICH6,TAFA5,,FANCI,FBXL12,FBXO16,FKBP4,ENSG00000280119,,GAS6-DT,GABRB2,GBP6,GLDC,GNRHR2,GOLGA1,ADGRA1,GPR19,GREB1L,GSTM5,GTF2H2,GULP1,HERC2P1,HIRIP3,HLA-DPB2,HMGB3P22,HOXA11,HTR3C,IGSF11,AJUBA,KCNA4,KCND3,KCNJ6,TESPA1,KIF18A,KLHL3,KRT72,KRTAP19-3,KRTAP2-4,KRTAP4-6,LARP6,DDC-AS1,LINC01783,,,,PRKAG2-AS1,LINC00645,RASSF8-AS1,TBX5-AS1,LINC00841,ATP11A-AS1,ENSG00000248540,BASP1-AS1,NAV2-AS5,,CIBAR1-DT,HHIP-AS1,MFF-DT,LINC01346,LRRC31,MAGEH1,ME1,MED22,MGC4859,PALS2,MT1E,MTERF1,MTFP1,IRF4,MYL5,MYOC,NCAM2,NRAD1,NPY2R,,NXPH2,OLIG2,OR10C1,OR10D3,OR1J4,OR7A5,PARG,PBX1,PCA3,PCDHGB6,PCDHGB8P,PHAX,PKLR,PKP3,PLCXD3,PLK4,POU3F2,PRICKLE2,PTHLH,PTPN5,RAD21L1,RAG1,RIC3,RIPPLY1,RPAP3,RUSC1-AS1,SCAND2P,SCNN1B,SDHAP1,SEMA4F,SERPINB13,SLC1A7,SLC25A1,SLC38A4,SLC4A10,SLCO2A1,SPRR4,SPRYD3,STATH,STON1,STRBP,STYK1,SYNC,TBXT,TACC2,TATDN3,THRA,TLR5,TMEM225,TMEM72,TRAF3IP2-AS1,TRAP1,TRMT61B,TSPAN5,TTC22,TTTY5,TUBB4A,UPK1A,VTCN1,WBP2NL,DNAI3,DNAI4,WNT2,YAP1,ZACN,ZBTB24,ZNF138,ZNF204P,ZNF208,ZNF28,ZNF320,ZNF354C,ZNF485,ZNF544,ZNF624,ZNF789 FOUNDER_NAMES