Affiliation:
1. From the Department of Immunology, The Scripps Research Institute, La Jolla, CA; and the Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA.
Abstract
AbstractIn septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1+/+ and Egr-1−/− mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1+/+ mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1−/− mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1+/+ mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1−/− mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor α in endotoxemic mice. Moreover, Egr-1+/+ and Egr-1−/− mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
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