ACTIVATION OF NF-κB VARIES IN DIFFERENT REGIONS OF THE GASTROINTESTINAL TRACT DURING ENDOTOXEMIA

Abstract

The transcription nuclear factor-κB (NF-κB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-κB is activated in the jejunal mucosa during endotoxemia, but the response of NF-κB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-κB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-κB 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-κB inhibitory proteins IκB-α and IκB-β were determined by Western blot analysis. Endotoxemia increased NF-κB 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-κB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IκB-α and IκB-β levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-κB. The results suggest that during endotoxemia, NF-κB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.