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Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

ABSTRACT: Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

PROVIDER: PRJNA318003 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3355790.fastq.gz	Fastqsanger.gz
	SRR3355781.fastq.gz	Fastqsanger.gz
	SRR3355791.fastq.gz	Fastqsanger.gz
	SRR3355782.fastq.gz	Fastqsanger.gz
	SRR3355792.fastq.gz	Fastqsanger.gz

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Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation (RNA-Seq)

Project description: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 numerous diseases associated with exacerbated inflammation. Here, we identify Topoisomerase 1 (Top1) as a critical positive regulator of RNA polymerase II (RNAPII) transcriptional activity at pathogen-induced genes. Notably, depletion or chemical inhibition of Top1 suppresses the host response against replicating Influenza and Ebola viruses as well as bacterial products. As a result, therapeutic pharmacological inhibition of Top1 protects mice from death in experimental models of chemical- and pathogen-induced 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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Project description: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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