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 proinflammatory 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.


OBJECTIVE
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.


CONCLUSIONS
The protective effects of the stress response in vivo might, at least in part, be due to inhibited NF-kappa B activation.
Pritts
T A
TA
Department of Surgery, University of Cincinnati, Ohio 45267-0558, USA.
Wang
Q
Q
Sun
X
X
Moon
M R
MR
Fischer
D R
DR
Fischer
J E
JE
Wong
H R
HR
Hasselgren
P O
PO
D000818:Animals; D018053:Arsenites; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000150:complications / Q000378:metabolism*; D006979:Hyperthermia, Induced; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D007583:Jejunum / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D017670:Sodium Compounds; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*
D018053:Arsenites; D016328:NF-kappa B; D017670:Sodium Compounds; C017947:sodium arsenite