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Am J Physiol Cell Physiol 275: C988-C994, 1998;
0363-6143/98 $5.00
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Vol. 275, Issue 4, C988-C994, October 1998

Cytokine-mediated PGE2 expression in human colonic fibroblasts

Edward C. Kim1, Yingting Zhu1, Valerie Andersen1, Daniela Sciaky2, H. James Cao2, Heather Meekins2, Terry J. Smith2, and Peter Lance1

1 Division of Gastroenterology, Department of Medicine, Veterans Affairs Medical Center and Buffalo General Hospital, State University of New York, Buffalo 14215; and 2 Division of Molecular and Cellular Medicine, Department of Medicine, Albany Medical College and Samuel S. Stratton Veterans Affairs Medical Center, Albany, New York 12208

We investigated prostanoid 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 PGE2 production was measured. PGH synthase-1 and -2 (PGHS-1 and -2) protein and mRNA expression were evaluated. Basal PGE2 levels were low in all cell types (0.15-6.47 ng/mg protein). Treatment for 24 h with interleukin-1beta (IL-1beta ; 10 ng/ml) or tumor necrosis factor-alpha (50 ng/ml), respectively, elicited maximal 25- and 6-fold inductions of PGE2 synthesis in CCD-18Co cultures and similar results in primary fibroblast cultures; maximal inductions with IL-1beta in colonic epithelial cell lines were from zero to fivefold. Treatment of CCD-18Co fibroblasts with IL-1beta caused maximal 21- and 53-fold increases, respectively, in PGHS-2 protein and mRNA levels without altering PGHS-1 expression. PGE2 (0.1 µmol/l) elicited a dramatic shape change in selected fibroblasts. Colonic fibroblasts are potentially important as cytokine targets and a source of and target for colonic prostanoids in vivo.

colorectal adenocarcinoma; primary fibroblast cultures; colon cancer cell lines; prostaglandin H synthases


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