Abstract
We investigated prostanoid biogenesis by human colonic fibroblasts (CCD-18Co cells and nine primary fibroblast cultures) exposed to a primary (cholic, CA) or a secondary (deoxycholic, DCA) bile acid. Basal PGE2 levels in CCD-18Co cultures and fibroblast strains initiated from normal and adenocarcinomatous colon, respectively, were 1.7 ± 0.3, 4.0 ± 2.0, and 15.0 ± 4.8 ng/mg protein. Peak levels 24 h after exposure to DCA (300 μM) rose, respectively, seven-, six- and sevenfold, but CA elicited no such responses. Increases in PGE2 synthesis were preceded by sequential increases in PGH synthase-2 mRNA and protein expression and were fully prevented by a nonselective (indomethacin) or a selective (celecoxib) nonsteroidal anti-inflammatory drug. DCA, but not CA, caused abrupt, transient increases in fibroblast intracellular Ca2+ concentration ([Ca2+]i) ∼1 min after exposure. Increased [Ca2+]i was required for DCA-mediated induction of PGE2 synthesis, and protein kinase C was a further essential component of this signaling pathway. Colonic fibroblasts may be a major target for prostanoid biogenesis induced by fecal bile acids and, potentially, other noxious actions of these agents.
Original language | English (US) |
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Pages (from-to) | G503-G510 |
Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 283 |
Issue number | 3 46-3 |
DOIs | |
State | Published - Sep 2002 |
Keywords
- Colorectal neoplasms
- Feces
- Mesenchymal cells
- Prostaglandin H synthases
ASJC Scopus subject areas
- Physiology
- Hepatology
- Gastroenterology
- Physiology (medical)