Polarized secretion of CXC chemokines by human intestinal epithelial cellsin response to Bacteroides fragilis enterotoxin: NF-kappa B plays a major role in the regulation of IL-8 expression

Enterotoxigenic B. fragilis, which produces a similar to 20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal infla mmation. To determine if epithelial cells can contribute to BFT-induced inf lammation, we assessed the expression of CXC chemokines by BFT-stimulated h uman intestinal epithelial cells. BFT stimulation increased expression of t he neutrophil chemoattractant and activators ENA-78, GRO-alpha, and IL-8. U p-regulated chemokine mRNA expression was paralleled by increased protein l evels. Activation of the IL-8 and NF-kappaB transcriptional reporters was i nhibited in cells cotransfected with the I kappaB kinase beta and IkB alpha superrepressor plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis, was released predominantly from the apical surface, CXC chemokines were predominantly secreted from the basolateral surface of BFT -treated epithelial cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon epithelial cells suggests that these chemokines can c ontribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.