Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.
The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.
Pritts
T A
TA
Department of Surgery, University of Cincinnati, and Shriners Hospital for Children, Cincinnati, Ohio, USA.
Moon
M R
MR
Wang
Q
Q
Hungness
E S
ES
Salzman
A L
AL
Fischer
J E
JE
Hasselgren
P O
PO
D000818:Animals; D003106:Colon / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism*; D019446:Endotoxemia / Q000235:genetics* / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009928:Organ Specificity
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA