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

The transcription nuclear factor-B-kappa (NF-B-kappa) regulates a large num ber of genes involved in the inflammatory response to sepsis and endotoxemi a. We recently found that NF-B-kappa is activated in the jejunal mucosa dur ing endotoxemia, but the response of NF-B-kappa in other parts of the gastr ointestinal tract is not known. We hypothesized that NF-B-kappa is differen tially activated in different regions of the gastrointestinal tract during endotoxemia. NF-B-kappa DNA binding activity was determined by electrophore tic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colo n from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-B -kappa inhibitory proteins IkappaB-alpha and IKB-beta were determined by We stern blot analysis. Endotoxemia increased NF-KB activity in mucosa of stom ach, jejunum, and ileum, with jejunum responding to smaller doses of endoto xin than the other parts of the gastrointestinal tract. NF-B-kappa DNA bind ing activity was not induced in colonic mucosa, even following administrati on of high doses of endotoxin, IKB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation o f NF-B-kappa. The results suggest that during endotoxemia, NF-B-kappa is ac tivated in mucosa of stomach and small intestine, but not in colon, and tha t the jejunum is particularly sensitive to endotoxin.