Induction of the stress response in vivo decreases nuclear factor-kappa B activity in jejunal mucosa of endotoxemic mice

Background: Results of previous studies suggest that the stress response protects cells and tissues by regulating pro-inflammatory mediators. The transcription factor nuclear factor-kappa B (NF-kappa B), normally sequestered in the cytoplasm by its inhibitory protein, I kappa B, regulates many genes involved in inflammatory responses to critical illness. Endotoxemia is associated with increased NF-kappa B activity in intestinal mucosa, but the effect of the stress response on endotoxin-induced NF-kappa B activation in intestinal mucosa is not known. Hypothesis: Induction of the stress response inhibits NF-kappa B DNA binding activity in jejunal mucosa during endotoxemia. Methods: The stress response was induced in mice by hyperthermia (42 degrees C) or injection with sodium arsenite (10 mg/kg). After 2 to 5 hours, mice were injected with endotoxin (lipopolysaccharide, 12.5 mg/kg) or a corresponding volume of sterile saline. One hour later, jejunal mucosa was harvested for preparation of nuclear and cytoplasmic extracts. Results: Mucosal levels of heat shock protein-72 increased after hyperthermia or treatment with sodium arsenite, consistent with induction of the stress response. The increase in NF-kappa B DNA binding activity and decrease in I kappa B-alpha levels seen after endotoxin injection were inhibited by previous induction of the stress response. Conclusion: The protective effects of the stress response in vivo might, at least in part, be due to inhibited NF-kappa B activation.