Polarized secretion of CXC chemokines by human intestinal epithelial cells in response toBacteroides fragilisenterotoxin: NF-κB plays a major role in the regulation of IL-8 expression

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Abstract
Enterotoxigenic B. fragilis, which produces a ∼20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal inflammation. To determine if epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of CXC chemokines by BFT-stimulated human intestinal epithelial cells. BFT stimulation increased expression of the neutrophil chemoattractant and activators ENA-78, GRO-α, and IL-8. Up-regulated chemokine mRNA expression was paralleled by increased protein levels. Activation of the IL-8 and NF-κB transcriptional reporters was inhibited in cells cotransfected with the IκB kinase β and IkBα 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 contribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.