Topoisomerases are ubiquitous enzymes that regulate the winding of DNA and thereby serve important roles in controlling gene expression. In Science, Marazzi and colleagues show that the topoisomerase Top1 positively regulates inflammation after challenge with microbial products, viruses or bacteria. Inhibition or knockdown of Top1 leads to lower expression of proinflammatory cytokines and interferon-stimulated genes and resistance to lethal inflammation triggered by viral or bacterial infection as well as by endotoxin challenge. Top1 seems to aid the expression of a highly select subset of genes encoding proinflammatory products—specifically those that require nucleosome remodeling for their activation. Mechanistically, Top1 facilitates the presence of the RNA polymerase RNAPII at specific genes that encode inflammatory products and thereby influences their expression. Clinically approved inhibitors of Top1 are already used in treating cancer but could potentially also be used for the management of harmful hyper-inflammation.

Science (28 April 2016) doi:10.1126/science.aad7993