Ca2+- and PKC-dependent stimulation of PGE2 synthesis by deoxycholic acid in human colonic fibroblasts

Yingting Zhu, Ping Hua, Shazia Rafiq, Eric J. Waffner, Michael E. Duffey, Peter Lance

Research output: Contribution to journalArticle

36 Scopus citations

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 languageEnglish (US)
Pages (from-to)G503-G510
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume283
Issue number3 46-3
DOIs
StatePublished - Sep 2002

Keywords

  • Colorectal neoplasms
  • Feces
  • Mesenchymal cells
  • Prostaglandin H synthases

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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