Cytokine-mediated PGE2 expression in human colonic fibroblasts

We investigatedprostanoid biogenesis in human colonic fibroblasts (CCD-18Co and 5 primary fibroblast cultures) and epithelial cell lines (NCM460, T84,HT-29, and LS 174T) and the effect of PGE₂ on fibroblast morphology.Cytokine-stimulated PGE₂production was measured. PGH synthase-1 and -2 (PGHS-1 and -2) proteinand mRNA expression were evaluated. BasalPGE₂ levels were low in all celltypes (0.15-6.47 ng/mg protein). Treatment for 24 h with interleukin-1 (IL-1; 10 ng/ml) or tumor necrosis factor- (50 ng/ml), respectively, elicited maximal 25- and 6-fold inductions ofPGE₂ synthesis in CCD-18Cocultures and similar results in primary fibroblast cultures; maximalinductions with IL-1 in colonic epithelial cell lines were from zeroto fivefold. Treatment of CCD-18Co fibroblasts with IL-1 causedmaximal 21- and 53-fold increases, respectively, in PGHS-2 protein andmRNA levels without altering PGHS-1 expression.PGE₂ (0.1 µmol/l) elicited adramatic shape change in selected fibroblasts. Colonic fibroblasts are potentially important as cytokine targets and a source of and targetfor colonic prostanoids in vivo.