STANDARD_NAME GSE20715_WT_VS_TLR4_KO_6H_OZONE_LUNG_UP SYSTEMATIC_NAME M4351 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE20715_WT_VS_TLR4_KO_6H_OZONE_LUNG_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in comparson of lung tissue from wild type mice subjected to ozone for 6 h vs that from TLR4 [GeneID=7099] deficient animal subjected to ozone for 6 h. DESCRIPTION_FULL We previously identified toll-like receptor 4 (Tlr4) as a candidate gene responsible for ozone (O3)-induced pulmonary hyperpermeability and inflammation. The objective of this study was to determine the mechanism through which TLR4 modulates O3-induced pulmonary responses and to utilize transcriptomics to determine TLR4 effector molecules. C3H/HeJ (HeJ; Tlr4 mutant) and C3H/HeOuJ (OuJ; Tlr4 normal), mice were exposed continuously to 0.3 ppm O3 or filtered air for 6, 24, 48 or 72 hr. Affymetrix Mouse430A_MOE gene arrays were used to analyze lung homogenates from HeJ and OuJ mice followed using a bioinformatic analysis. Inflammation was assessed by bronchoalveolar lavage and molecular analysis by ELISA, immunoblotting, and transcription factor activity. TLR4 signals through both the MYD88-dependent and independent pathways in OuJ mice, which involves MAP kinase activation, NF-kappaB, AP-1, and KC. Microarray analyses identifiedTLR4 responsive genes for strain and time in OuJ versus HeJ mice (p<0.05). One significantly upregulated cluster of genes in OuJ were the heat shock proteins (Hspa1b; Hsp70), Hsp90ab1). Furthermore, O3-induced expression of HSP70 protein was increased in OuJ compared to HeJ mice following 24-48 h O3. Moreover, BAL polymorphonuclear leukocytes (PMN) and total protein were significantly reduced in response to O3 in Hspa1a/Hspa1btm1Dix (Hsp70-/-) compared to Hsp70+/+ mice (p<0.05). TLR4 signaling (MYD88-dependent), ERK1/2, AP-1 activity, and KC protein content were also significantly reduced after O3 exposure in Hsp70-/- compared to Hsp70+/+ mice (p<0.05). These studies suggest that HSP70 is involved in the regulation of O3-induced lung inflammation through the TLR4 pathway and provide evidence that HSP70 is an endogenous in vivo TLR4 ligand. PMID 21543283 GEOID GSE20715 AUTHORS Bauer AK,Rondini EA,Hummel KA,Degraff LM,Walker C,Jedlicka AE,Kleeberger SR CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE20715_2073_200_UP FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABCA2,ABCD2,ACD,ACER2,ACTN4,ADD3,AKIRIN1,AKT3,ANKRD1,ANXA6,APTX,AREG,ASAH2,ATG7,ATP1B3,AXL,B4GALT4,BCL2,BFSP1,BGN,C12orf45,C18orf10,C1orf123,C1orf9,C21orf59,C2orf65,CARHSP1,CBY1,CD302,CD8B,CDK5R1,CHGA,CHST2,CLCN7,COL15A1,COL16A1,COL4A3,COPS3,COPZ2,COX5A,CRADD,CTLA4,CTSS,CTTNBP2NL,CXCR7,CYBB,DERL3,DNAJA2,DNAJC1,EDNRB,EEF1E1,EIF2AK4,EIF4E,EPB41L2,EPHA3,EXOSC10,EXOSC2,FANCL,FBXO2,FIG4,FN1,FTSJD2,GALM,GCLC,GHDC,GOLGA3,GPR3,GPR89B,H2AFX,HDAC6,HMGCR,HSDL2,HSPA5,HTRA1,ICMT,IKZF1,IL18BP,IMPACT,ITGAL,ITM2B,JKAMP,KAT2A,KCNH3,KCNJ11,KCNJ4,KCNJ5,KIAA1191,KIF20A,KIF3C,KLHL20,LAIR1,LASS5,LCN8,LEPROT,LGALS9B,LRRK2,MAPK14,MDH2,MR1,MRPL42,MS4A8B,MTMR6,MYEF2,MYH9,MYL9,NCOA1,NFATC2IP,NOP56,NPHS2,NPNT,NT5C2,NUP160,OSGIN2,OTUD5,PCYOX1,PDE6C,PHF20,PHOX2A,PIK3AP1,PILRB,PIP4K2B,PKNOX2,PLXNC1,PMP22,POLR1E,POSTN,PPIL4,PRELP,PRKAR1B,PRKAR2A,PRKCA,PROS1,PRPF8,PRPSAP2,PSEN1,PSMB7,PSMD8,PTCD1,PTGFR,PTGFRN,PTPLA,PTPRA,RANBP17,RBP3,RCAN1,RIOK2,RNF149,RNF4,RNGTT,ROBO1,RPS6KB2,RRM1,RRP15,SAG,SARDH,SDC3,SEPHS2,SEPT2,SERPINA10,SERPINF1,SERTAD3,SETD7,SGCB,SGOL1,SH2D1B,SLC12A5,SLC2A9,SLC31A2,SLC38A10,SMAD1,SMYD1,SNX10,SORCS1,SQSTM1,SRPX,STAU1,STRN3,SYT12,TBRG1,TCF25,TLR2,TMCC3,TMCO1,TMED7,TMEM2,TMEM66,TMEM85,TSPAN12,TUBB4,TWSG1,TYRO3,UBA3,UBAP2L,UBE2D3,UBLCP1,UGGT2,VBP1,VMA21,WDR61,ZP1 GENE_SYMBOLS ABCA2,ABCD2,ACD,ACER2,ACTN4,ADD3,AKIRIN1,AKT3,ANKRD1,ANXA6,APTX,AREG,ASAH2,ATG7,ATP1B3,AXL,B4GALT4,BCL2,BFSP1,BGN,NOPCHAP1,TPGS2,CZIB,SUCO,CFAP298,M1AP,CARHSP1,CBY1,CD302,CD8B,CDK5R1,CHGA,CHST2,CLCN7,COL15A1,COL16A1,COL4A3,COPS3,COPZ2,COX5A,CRADD,CTLA4,CTSS,CTTNBP2NL,ACKR3,CYBB,DERL3,DNAJA2,DNAJC1,EDNRB,EEF1E1,EIF2AK4,EIF4E,EPB41L2,EPHA3,EXOSC10,EXOSC2,FANCL,FBXO2,FIG4,FN1,CMTR1,GALM,GCLC,GHDC,GOLGA3,GPR3,GPR89B,H2AX,HDAC6,HMGCR,HSDL2,HSPA5,HTRA1,ICMT,IKZF1,IL18BP,IMPACT,ITGAL,ITM2B,JKAMP,KAT2A,KCNH3,KCNJ11,KCNJ4,KCNJ5,KIAA1191,KIF20A,KIF3C,KLHL20,LAIR1,CERS5,LCN8,LEPROT,LGALS9B,LRRK2,MAPK14,MDH2,MR1,MRPL42,MS4A8,MTMR6,MYEF2,MYH9,MYL9,NCOA1,NFATC2IP,NOP56,NPHS2,NPNT,NT5C2,NUP160,OSGIN2,OTUD5,PCYOX1,PDE6C,PHF20,PHOX2A,PIK3AP1,PILRB,PIP4K2B,PKNOX2,PLXNC1,PMP22,POLR1E,POSTN,PPIL4,PRELP,PRKAR1B,PRKAR2A,PRKCA,PROS1,PRPF8,PRPSAP2,PSEN1,PSMB7,PSMD8,PTCD1,PTGFR,PTGFRN,HACD1,PTPRA,RANBP17,RBP3,RCAN1,RIOK2,RNF149,RNF4,RNGTT,ROBO1,RPS6KB2,RRM1,RRP15,SAG,SARDH,SDC3,SEPHS2,SEPTIN2,SERPINA10,SERPINF1,SERTAD3,SETD7,SGCB,SGO1,SH2D1B,SLC12A5,SLC2A9,SLC31A2,SLC38A10,SMAD1,SMYD1,SNX10,SORCS1,SQSTM1,SRPX,STAU1,STRN3,SYT12,TBRG1,TCF25,TLR2,TMCC3,TMCO1,TMED7,CEMIP2,SARAF,EMC4,TSPAN12,TUBB4A,TWSG1,TYRO3,UBA3,UBAP2L,UBE2D3,UBLCP1,UGGT2,VBP1,VMA21,SKIC8,ZP1 FOUNDER_NAMES