CYTOKINE-MEDIATED PGE(2) EXPRESSION IN HUMAN COLONIC FIBROBLASTS

We investigated prostanoid biogenesis in human colonic fibroblasts (CC D-18Co and 5 primary fibroblast cultures) and epithelial cell lines (N CM460, T84, HT-29, and LS 174T) and the effect of PGE(2) on fibroblast morphology. Cytokine-stimulated PGE(2) production was measured. PGH s ynthase-1 and -2 (PGHS-1 and -2) protein and mRNA expression were eval uated. Basal PGE(2) levels were low in all cell types (0.15-6.47 ng/mg protein). Treatment for 24 h with interleukin-1 beta (IL-1 beta; 10 n g/ml) or tumor necrosis factor-alpha (50 ng/ml), respectively, elicite d maximal 25- and 6-fold inductions of PGE(2) synthesis in CCD-18Co cu ltures and similar results in primary fibroblast cultures; maximal ind uctions with IL-1 beta in colonic epithelial cell lines were from zero to fivefold. Treatment of CCD-18Co fibroblasts with IL-1 beta caused maximal 21- and 53-fold increases, respectively, in PGHS-2 protein and mRNA levels without altering PGHS-1 expression. PGE(2) (0.1 mu mol/l) elicited a dramatic shape change in selected fibroblasts. Colonic fib roblasts are potentially important as cytokine targets and a source of and target for colonic prostanoids in vivo.