Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 27, 2016
- Source ID
- 10.1126/science.aad7993
Entities
People
- Adolfo García-Sastre
- Alex Rialdi
- Alexander Bukreyev
- Arvin Cesar Lagda
- Cesar Munoz-fontela
- Chris Benner
- Christopher F Basler
- Colette Pietzsch
- Giorgi Metreveli
- Harm Van Bakel
- Ivan Marazzi
- Jessica Sook Yuin Ho
- Jian Jin
- Laura Campisi
- Luis Martinez-gil
- Matthew T Weirauch
- Megan Edwards
- Miriam Merad
- Nan Zhao
- Nicole Bouvier
- Romain Fenouil
- Stefan Jordan
- Sven Heinz
- Xiaoting Chen
- Zuleyma Peralta
Organizations
- Agency for Science, Technology and Research
- Cincinnati Children's Hospital Medical Center
- Icahn School of Medicine at Mount Sinai
- Leibnitz-Institute of Virology
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Salk Institute for Biological Studies
- United States Department of Defense
- United States Public Health Service
- University of California, San Diego
- University of Texas Medical Branch
- University of Valencia