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RESEARCH PRODUCT
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation
Christopher BennerJian JinArvin Cesar LagdaAlexander BukreyevJessica Sook Yuin HoGiorgi MetreveliLuis Martínez-gilLuis Martínez-gilStefan JordanColette PietzschNan ZhaoAlex RialdiHarm Van BakelRomain FenouilLaura CampisiAdolfo García-sastreMatthew T. WeirauchCésar Muñoz-fontelaMiriam MeradZuleyma PeraltaChristopher F. BaslerXiaoting ChenSven HeinzSven HeinzIvan MarazziNicole M. BouvierMegan R. Edwardssubject
0301 basic medicineTranscription GeneticType IInbred C57BLmedicine.disease_causeSendai virusMicePiperidinesTranscription (biology)Influenza A virusInnate2.1 Biological and endogenous factorsPositive Transcriptional Elongation Factor BAetiologyMultidisciplinaryAzepinesStaphylococcal InfectionsEbolavirusInfectious DiseasesDNA Topoisomerases Type IInfluenza A virusEbolaHost-Pathogen InteractionsPneumonia & InfluenzaRNA Polymerase IImedicine.symptomInfectionTranscriptionStaphylococcus aureusGeneral Science & TechnologyInflammationBiologyVaccine Related03 medical and health sciencesImmune systemGeneticImmunityBiodefenseGeneticsmedicineAnimalsHumansGeneFlavonoidsInflammationInnate immune systemPreventionHEK 293 cellsImmunityInterferon-betaHemorrhagic Fever EbolaTriazolesImmunity InnateMice Inbred C57BLEmerging Infectious DiseasesGood Health and Well BeingHEK293 Cells030104 developmental biologyGene Expression RegulationImmunologyCancer researchHemorrhagic FeverCamptothecinTopoisomerase I InhibitorsTopotecanDNA Topoisomerasesdescription
Unwinding DNA and unleasing inflammation Fighting infections often comes with collateral damage, which sometimes can be deadly. For instance, in septic shock, the overwhelming release of inflammatory mediators drives multi-organ failure. Rialdi et al. now report a potential new therapeutic target for controlling excessive inflammation: the DNA unwinding enzyme topoisomerase I (Top1) (see the Perspective by Pope and Medzhitov). Upon infection, Top1 specifically localizes to the promoters of pathogen-induced genes and promotes their transcription by helping to recruit RNA polymerase II. Pharmacological inhibition of Top1 in a therapeutic setting increased survival in several mouse models of severe microbially induced inflammation. Science , this issue p. 10.1126/science.aad7993 ; see also p. 1058
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-11-03 | Science |