STANDARD_NAME GSE3565_DUSP1_VS_WT_SPLENOCYTES_POST_LPS_INJECTION_UP SYSTEMATIC_NAME M6332 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE3565_DUSP1_VS_WT_SPLENOCYTES_POST_LPS_INJECTION_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in spleen from mice injected with LPS: DUSP1 [GeneID=1843] knockout versus wildtype. DESCRIPTION_FULL Activation of the Mitogen activated protein kinase (MAPK) cascade following Toll-like receptor (TLR) stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase Dual specificity phosphatase-1 (DUSP1) as an essential endogenous regulator of the inflammatory response to LPS. DUSP1-deficient (DUSP1-/-) bone marrow derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1-/- mice with LPS caused increased lethality and overshooting production of IL-6 and TNF-alpha. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, that includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4 and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, IFN-gamma and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock. PMID 16380512 GEOID GSE3565 AUTHORS Hammer M,Mages J,Dietrich H,Servatius A,Howells N,Cato AC,Lang R CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE3565_2624_200_UP FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1110004E09Rik,1700025G04Rik,1700092C17Rik,2900006K08Rik,4632427E13Rik,ABLIM1,ACTN1,ADAM19,AEN,AFP,AGPAT5,AHCY,AKAP10,AKAP13,AKAP9,ARHGAP9,ARHGEF1,ASB15,ATP11B,ATP5C1,BC016423,BC021614,BRD4,BTLA,CBL,CCDC162,CCDC64,CCNL2,CCR7,CDH1,CDK5RAP1,CIRH1A,CLDND1,CLEC2D,COMMD2,CSNK1E,CSNK1G1,CSNK1G3,DAPL1,DDX3Y,DKC1,EEF1B2,EG547347,EIF3H,EIF3J,EMD,ERAP1,ETNK1,FAAH,FAM134B,FAM46A,FAM55A,FAM96A,FCHSD2,FRMD8,GLUD1,GM11599,GM11878,GM12109,GM12541,GM13194,GM14165,GM4005,GM5121,GM5215,GM5257,GM5470,GM5779,GM6590,GM6689,GM7059,GM7246,GM7966,GM8371,GM9372,GNL3,GPHN,GPR15,HNRNPU,HSPA9,HTATSF1,IFRD2,IKBKE,IL2,IL4RA,IL6ST,INADL,INPP4B,INSR,INTS1,IPO4,LOC630837,LPHN3,LTV1,LYST,MAGOHB,MDN1,METAPL1,MIPEP,MKI67IP,MRE11A,MRPS36,MTHFD1,MTMR15,MYB,MYC,MYOZ1,NCOA6,NEDD4L,NEFH,NEURL3,NFATC2IP,NMD3,NPM1,NSG2,NUP155,NUP160,OLFR1100,OLFR1461,OLFR615,OLFR663,OLFR860,OLFR877,PA2G4,PARP8,PDK1,PDS5B,PGF,PHF12,PIM2,PLCB2,PLEKHA1,POLE2,POLR3E,PPP1R3C,PRDX6,PRMT3,PRPS2,PURB,RAPGEF6,RCL1,RCN3,RLIM,RNF144A,RPL10A,RPL13,RPL17,RPL18,RPL19,RPL23A,RPL24,RPL27,RPL29,RPL32,RPL35A,RPL36,RPL36A,RPL8,RPLP0,RPLP1,RPS10,RPS15,RPS15A,RPS2,RPS20,RPS26,RPS5,SCAPER,SEC61A2,SELL,SIDT1,SMEK2,SND1,SNRK,SOCS3,SPINK8,SRM,SSBP2,SZT2,TAF1D,THADA,THUMPD2,TLR1,TLR6,TMEM154,TMEM38B,TNFAIP8,TNFSF8,TRAF1,TREML2,TSEN2,TTC13,TTLL12,TWISTNB,U2AF2,VPS13A,WDR77,XCL1,ZFP280D,ZSCAN12 GENE_SYMBOLS ,,,,,ABLIM1,ACTN1,ADAM19,AEN,AFP,AGPAT5,AHCY,AKAP10,AKAP13,AKAP9,ARHGAP9,ARHGEF1,ASB15,ATP11B,ATP5F1C,TASOR2,GSTP1,BRD4,BTLA,CBL,CCDC162P,BICDL1,CCNL2,CCR7,CDH1,CDK5RAP1,UTP4,CLDND1,CLEC2D,COMMD2,CSNK1E,CSNK1G1,CSNK1G3,DAPL1,DDX3Y,DKC1,EEF1B2,,EIF3H,EIF3J,EMD,ERAP1,ETNK1,FAAH,RETREG1,TENT5A,NXPE1,CIAO2A,FCHSD2,FRMD8,GLUD1,,,,,,,,,,,,,,,,,,,,GNL3,GPHN,GPR15,HNRNPU,HSPA9,HTATSF1,IFRD2,IKBKE,IL2,,IL6ST,PATJ,INPP4B,INSR,INTS1,IPO4,,ADGRL3,LTV1,LYST,MAGOHB,MDN1,,MIPEP,NIFK,MRE11,MRPS36,MTHFD1,FAN1,MYB,MYC,MYOZ1,NCOA6,NEDD4L,NEFH,NEURL3,NFATC2IP,NMD3,NPM1,NSG2,NUP155,NUP160,,,,,,,PA2G4,PARP8,PDK1,PDS5B,PGF,PHF12,PIM2,PLCB2,PLEKHA1,POLE2,POLR3E,PPP1R3C,PRDX6,PRMT3,PRPS2,PURB,RAPGEF6,RCL1,RCN3,RLIM,RNF144A,RPL10A,RPL13,RPL17,RPL18,RPL19,RPL23A,RPL24,RPL27,RPL29,RPL32,RPL35A,RPL36,RPL36A,RPL8,RPLP0,RPLP1,RPS10,RPS15,RPS15A,RPS2,RPS20,RPS26,RPS5,SCAPER,SEC61A2,SELL,SIDT1,PPP4R3B,SND1,SNRK,SOCS3,SPINK8,SRM,SSBP2,SZT2,TAF1D,THADA,THUMPD2,TLR1,TLR6,TMEM154,TMEM38B,TNFAIP8,TNFSF8,TRAF1,TREML2,TSEN2,TTC13,TTLL12,POLR1F,U2AF2,VPS13A,WDR77,XCL1,,ZSCAN12 FOUNDER_NAMES