The Role of the E2F1 Transcription Factor in the Innate Immune Response to Systemic LPS

Overview

Journal Am J Physiol Lung Cell Mol Physiol

Publisher American Physiological Society

Specialties Cell Biology
Molecular Biology
Physiology
Pulmonary Medicine

Date 2012 Jun 19

PMID 22707615

Citations 21

Authors

Laura A Warg

Judy L Oakes

Rachel Burton

Amanda J Neidermyer

Holly R Rutledge

Steve Groshong

David A Schwartz

Ivana V Yang

Affiliations

Soon will be listed here.

Abstract

Previous publications from our and other groups identified E2F1 as a transcription factor involved in the regulation of inflammatory response to Toll-like receptor ligands including LPS. In this study, we challenged E2F1-deficient mice with LPS systemically and demonstrated decreased survival despite attenuated inflammatory response compared with controls. Gene expression profiling of liver tissue identified a dampened transcriptional response in the coagulation cascade in B6;129(E2F1-/-) compared with B6x129 F2 mice. These data were further corroborated by increased prothrombin time, activated partial thromboplastin time, and fibrin split products in the blood of E2F1-deficient mice, suggesting disseminated intravascular coagulation as a consequence of uncontrolled sepsis providing at least a partial explanation for their decreased survival despite attenuated inflammatory response. To identify novel miRNAs involved in the innate immune response to LPS, we also performed miRNA profiling of liver tissue from B6;129(E2F1-/-) and B6x129 F2 mice treated with LPS systemically. Our analysis identified a set of miRNAs and their mRNA targets that are significantly differentially regulated in E2F1-deficient but not control mice including let-7g, miR-101b, miR-181b, and miR-455. These miRNAs represent novel regulators of the innate immune response. In summary, we used transcriptional and miRNA profiling to characterize the response of E2F1-deficient mice to systemic LPS.

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