Enprostil, a Prostaglandin‐E 2 Analogue, Inhibits Interleukin‐8 Production of Human Colonic Epithelial Cell Lines

We previously reported that intracolonic administration of enprostil, a prostaglandin‐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 chemoattractant‐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 line (HT‐29) to investigate enprostil effects on the IL‐8 production of intestinal epithelial cells stimulated by various stimulants. In a MTT assay, concentrations 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‐1β (IL‐1β) or lipopolysaccharide (LPS), but did not suppress this response when cells were stimulated with tumour necrosis factor (TNF)‐α. These results suggest that enprostil affects a point in the pathway between the IL‐1 receptor or LPS receptor and nuclear factor‐κB(NF‐κB), without affecting the pathway between the TNF receptor and NF‐κB, with the latter factor being required for the IL‐8 gene transcription. The therapeutic effect of exogenous enprostil on DSS colitis may involve the inhibition of IL‐8 production in colonic epithelial cells stimulated by IL‐1β or LPS.