Journal
SHOCK
Volume 14, Issue 2, Pages 118-122Publisher
BIOMEDICAL PRESS
DOI: 10.1097/00024382-200014020-00007
Keywords
I kappa B-alpha; I kappa B-beta; sepsis; inflammation; intestine; mucosa
Funding
- NIGMS NIH HHS [1T32GM08478] Funding Source: Medline
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The transcription nuclear factor-B-kappa (NF-B-kappa) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-B-kappa is activated in the jejunal mucosa during endotoxemia, but the response of NF-B-kappa in other parts of the gastrointestinal tract is not known. We hypothesized that NF-B-kappa is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-B-kappa 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-B-kappa inhibitory proteins IkappaB-alpha and IKB-beta were determined by Western blot analysis. Endotoxemia increased NF-KB 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-B-kappa DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin, IKB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-B-kappa. The results suggest that during endotoxemia, NF-B-kappa is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.
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