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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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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.

2016-07-11 | GSE80131 | GEO

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

2016-07-11 | GSE80129 | GEO

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

Project description: Not available

| S-EPMC5193222 | biostudies-literature

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-07-11 | GSE80132 | GEO

PD-1 Protects Bystander-Activated T Cells from Activation-Induced Cell Death

Project description:PD-1 is a critical T-cell checkpoint that suppresses nonantigen-specific bystander memory T-cell activation and proliferation but also protects them from apoptotic activation-induced cell death.

2023-10-25 | GSE199615 | GEO

EFHD2 Suppresses Intestinal Inflammation by Blocking Intestinal Epithelial Cell TNFR1 Internalization and Cell Death

Project description:Death of intestinal epithelial cells (IECs) is important in the pathological process of intestinal inflammatory diseases. TNF acts as one pathogenic driver for inducing IEC death and substantial intestinal inflammation. However, the physiological protective mechanisms for suppressing TNF-induced IEC death remain poorly understood. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects the intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin to suppress the phosphorylation of Cofilin, leading to the inhibition of TNF receptor Ⅰ (TNFR1) internalization and TNF-induced apoptosis. Our findings define EFHD2 as an endogenous suppressor of IEC death to protect intestine inflammation, providing new insight to the regulation of death receptor signaling and control of intestinal inflammatory diseases.

2024-01-14 | PXD048587 | iProX

Desmosterol suppresses inflammasome activation and protects against atherosclerosis

Project description:Desmosterol suppresses inflammasome activation and protects against atherosclerosis

| PRJNA723043 | ENA

Desmosterol suppresses inflammasome activation and protects against atherosclerosis II

Project description:Desmosterol suppresses inflammasome activation and protects against atherosclerosis II

| PRJNA732064 | ENA

Homo sapiens

Project description:Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation (ChIP-Seq)

| PRJNA318007 | ENA

Homo sapiens

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