Role of prostaglandin H synthase-2-mediated conversion of arachidonic acid in controlling 3T6 fibroblast growth.

TitleRole of prostaglandin H synthase-2-mediated conversion of arachidonic acid in controlling 3T6 fibroblast growth.
Publication TypeJournal Article
Year of Publication1997
AuthorsMartinez J, Sanchez T, Moreno JJ
JournalAm J Physiol
Volume273
Issue5
PaginationC1466-71
Date Published1997 11
ISSN0002-9513
Keywords3T3 Cells, Animals, Arachidonic Acid, Cell Division, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Dexamethasone, Dinoprostone, DNA, Indans, Isoenzymes, Ketoprofen, Kinetics, Mice, Prostaglandin-Endoperoxide Synthases
Abstract

The specific role(s) of arachidonic acid (AA) and its metabolites in the signaling pathways that regulated fibroblast growth was studied. A Western blot analysis demonstrated that prostaglandin H synthase-2 (PGHS-2) was expressed by 3T6 fibroblast cultures in RPMI 1640 supplemented with fetal calf serum (10%). Dexamethasone, which inhibits AA release and PGHS-2 expression, significantly reduced cell proliferation. Ketoprofen, a dual cyclooxygenase inhibitor, and CGP-28238, a specific PGHS-2 inhibitor, reduced fibroblast proliferation in a dose-dependent manner. These drugs also reduced [3H]thymidine incorporation into the DNA of fibroblasts. These effects were correlated with a decrease in prostaglandin (PG) E2 levels in the cell medium. However, piroxicam at doses that selectively inhibit PGHS-1 did not have a significant effect on fibroblast proliferation. Finally, we showed that the antiproliferative effect of dexamethasone and PGHS-2 inhibitors was significantly antagonized when PGE2 was added to the culture medium. Our results suggest that PGHS-2 and prostaglandins such as PGE2 might play an important role in the regulation of 3T6 fibroblast growth stimulated by growth factors of serum.

DOI10.1152/ajpcell.1997.273.5.C1466
Alternate JournalAm J Physiol
PubMed ID9374630
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Teresa Sanchez, Ph.D.

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