Enprostil, a prostaglandin-E-2 analogue, inhibits interleukin-8 productionof human colonic epithelial cell lines

We previously reported that intracolonic administration of enprostil, a pro staglandin-E-2 (PGE(2)) analogue, had therapeutic effects on acute colitis induced in rodents by dextran sulfate sodium (DSS). In addition, production of growth-regulated gene product/cytokine-induced neutrophil chemoattracta nt-1 [GRO/CINC-1; an interleukin(IL)-8 like cytokine] was suppressed in the inflamed tissues. In the present study we used a human colon cancer cell l ine (HT-29) to investigate enprostil effects on the IL-8 production of inte stinal epithelial cells stimulated by various stimulants. In a MTT assay, c oncentrations of enprostil > 10(-5)M had cytotoxitic effects on HT-29 cells . Furthermore, 10(-6) M enprostil suppressed IL-8 production in HT-29 cells , SW620 and CaCo2 stimulated with interleukin-1 beta (IL-1 beta) or lipopol ysaccharide (LPS), but did not suppress this response when cells were stimu lated with tumour necrosis factor (TNF)-alpha. These results suggest that e nprostil affects a point in the pathway between the IL-1 receptor or LPS re ceptor and nuclear factor-kappaB(NF-kappaB), without affecting the pathway between the TNF receptor and NF-kappaB, with the latter factor being requir ed for the IL-8 gene transcription. The therapeutic effect of exogenous enp rostil on DSS colitis may involve the inhibition of IL-8 production in colo nic epithelial cells stimulated by IL-1 beta or LPS.