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Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation.
Rialdi, Alex; Campisi, Laura; Zhao, Nan; Lagda, Arvin Cesar; Pietzsch, Colette; Ho, Jessica Sook Yuin; Martinez-Gil, Luis; Fenouil, Romain; Chen, Xiaoting; Edwards, Megan; Metreveli, Giorgi; Jordan, Stefan; Peralta, Zuleyma; Munoz-Fontela, Cesar; Bouvier, Nicole; Merad, Miriam; Jin, Jian; Weirauch, Matthew; Heinz, Sven; Benner, Chris; van Bakel, Harm; Basler, Christopher; García-Sastre, Adolfo; Bukreyev, Alexander; Marazzi, Ivan.
Afiliação
  • Rialdi A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Campisi L; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Zhao N; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lagda AC; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Pietzsch C; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Ho JSY; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Martinez-Gil L; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Fenouil R; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Chen X; Department of Pathology, Microbiology, and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Edwards M; Laboratory of Methyltransferases in Development and Disease, Institute of Molecular and Cell Biology, Singapore.
  • Metreveli G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Jordan S; Department of Biochemistry and Molecular Biology, Universitat de Valencia, Valencia, Spain.
  • Peralta Z; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Munoz-Fontela C; Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • Bouvier N; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Merad M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Jin J; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Weirauch M; Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Heinz S; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Benner C; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • van Bakel H; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Basler C; Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • García-Sastre A; Department of Structural and Chemical Biology, Department of Oncological Sciences, and Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Bukreyev A; Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • Marazzi I; Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Science ; 352(6289): aad7993, 2016 May 27.
Article em En | MEDLINE | ID: mdl-27127234
ABSTRACT
The host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of diseases associated with exacerbated inflammation. We identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes. Depletion or chemical inhibition of Top1 suppresses the host response against influenza and Ebola viruses as well as bacterial products. Therapeutic pharmacological inhibition of Top1 protected mice from death in experimental models of lethal inflammation. Our results indicate that Top1 inhibition could be used as therapy against life-threatening infections characterized by an acutely exacerbated immune response.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Regulação da Expressão Gênica / DNA Topoisomerases Tipo I / Interações Hospedeiro-Patógeno / Inibidores da Topoisomerase I / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Science Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Regulação da Expressão Gênica / DNA Topoisomerases Tipo I / Interações Hospedeiro-Patógeno / Inibidores da Topoisomerase I / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Science Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos