A ${sim}20;kDa$ heat-labile toxin (EFT) produced by enterotoxigenic B. fragilis induces chemokine responses that may be associated with mucosal inflammation. To determine whether epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of cyclooxygenase (COX)-2 in BFT-stimulated human intestinal epithelial cells. Human intestinal epithelial cell lines, HT-29 and Caco-2, were incubated with purified BFT. COX-2 mRNA and protein expression were measured by quantitative RT-PCR and Western blot analysis, respectively. BFT increased expression of COX-2, not that of COX-1, in human intestinal epithelial cell lines. Up-regulated COX-2 expression was paralleled by increased prostaglandin $E_2;(PGE_2)$ production measured by the radioimmunoassay. $PGE_2$ was predominantly secreted from the basolateral surface of BFT-treated epithelial cells, whereas lactate dehydrogenase was released predominantly from the apical surface. Moreover, the COX-2 expression and $PGE_2$ production were significantly suppressed when NF-${kappa}B$ activity was inhibited. The basolateral secretion of $PGE_2$ by up-regulated COX-2 in the BFT-stimulated colon epithelial cells seems to contribute to the inflammatory response in the underlying intestinal mucosa.