Activation of NF-κB varies in different regions of the gastrointestinal tract during endotoxemia

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.