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

Ca2+- and PKC-dependent stimulation of PGE2 synthesis by deoxycholic acid in human colonic... 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 PGE 2 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 PGE 2 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 Ca 2+ concentration (Ca 2+ i ) ∼1 min after exposure. Increased Ca 2+ i was required for DCA-mediated induction of PGE 2 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. colorectal neoplasms feces mesenchymal cells prostaglandin H synthases Footnotes Address for reprint requests and other correspondence: P. Lance, Arizona Health Sciences Center and Cancer Center, P.O. Box 245028, 1501 N. Campbell Ave., Tucson, AZ 85724-5028 (E-mail: plance@azcc.arizona.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. May 1, 2002;10.1152/ajpgi.00525.2001 Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

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

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References (49)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00525.2001
pmid
12181161
Publisher site
See Article on Publisher Site

Abstract

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 PGE 2 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 PGE 2 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 Ca 2+ concentration (Ca 2+ i ) ∼1 min after exposure. Increased Ca 2+ i was required for DCA-mediated induction of PGE 2 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. colorectal neoplasms feces mesenchymal cells prostaglandin H synthases Footnotes Address for reprint requests and other correspondence: P. Lance, Arizona Health Sciences Center and Cancer Center, P.O. Box 245028, 1501 N. Campbell Ave., Tucson, AZ 85724-5028 (E-mail: plance@azcc.arizona.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. May 1, 2002;10.1152/ajpgi.00525.2001 Copyright © 2002 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver Physiology – The American Physiological Society

Published: Sep 1, 2002

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