The stress response decreases NF-κB activation in liver of endotoxemic mice

Timothy A. Pritts, Quan Wang, Xiaoyan Sun, David R. Fischer, Eric S. Hungness, Josef E. Fischer, Hector R. Wong, Per Olof Hasselgren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Recent studies suggest that the stress (heat shock) response protects cells and tissues from inflammatory and other noxious insults. The transcription factor nuclear factor-kappa B (NF-κB), normally sequestered in the cytoplasm by its inhibitory protein IκB, regulates many genes involved in the inflammatory response to critical illness. Endotoxemia is associated with increased NF-κB activity in liver but the effect of the stress response on endotoxin-induced NF-κB activation in the liver is not known. We hypothesized that the stress response inhibits NF-κB DNA binding activity in liver during endotoxemia. The stress response was induced in mice by hyperthermia (42°C for 3 min) or sodium arsenite (10 mg/kg) and resulted in increased hepatic heat shock protein-72 levels. After induction of the stress response, mice were injected subcutaneously with endotoxin (12.5 mg/kg) or a corresponding volume of sterile saline. NF-κB DNA binding activity in the nuclear fraction of liver tissue increased and cytoplasmic IκB-a levels decreased after endotoxin injection, with a maximal effect seen at 60 min. The endotoxin-induced increase in NF-κB DNA binding activity and decrease in IκB-a levels were inhibited by prior induction of the stress response. In additional experiments, treatment of mice with sodium arsenite after induction of endotoxemia blunted the increase in NF-κB activity, indicating a therapeutic potential of sodium arsenite, in addition to its preventive effect. The present results suggest that the protective effects of the stress response in vivo may, at least in part, be due to inhibited NF-κB activation.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalShock
Volume18
Issue number1
DOIs
StatePublished - Dec 1 2002

Keywords

  • Inflammation
  • Sepsis
  • Sodium arsenite
  • Transcription factor
  • heat shock

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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