Arachidonic acid metabolism in normal and transformed rat tracheal epithelial cells and its possible role in the regulation of cell proliferation.
The objectives of our investigations were to characterize the profile of arachidonic acid metabolites produced by cultured rat tracheal epithelial cells, and to determine whether or not transformation of these cells causes major qualitative or quantitative changes in arachidonic acid metabolism and whether arachidonic acid metabolites play an important role in the regulation of proliferation of rat tracheal cells. Our studies showed that prostaglandin E2 was the only major prostanoid produced by normal and transformed rat tracheal epithelial cells. When stimulated with calcium ionophore A23187, 12-O-tetradecanoylphorbol 13-acetate, arachidonic acid, or serum, the cultures produced small amounts of thromboxane B2, prostaglandin F2 alpha, and hydroxyeicosatetraenoic acid(s) in addition to prostaglandin E2. Mitogenesis studies showed that none of the peptide growth factors tested stimulated either prostaglandin E2 production or DNA synthesis. Fetal bovine serum, on the other hand, stimulated both. 12-O-Tetradecanoylphorbol 13-acetate and arachidonic acid stimulated prostaglandin E2 production but caused no increase in DNA synthesis. Dexamethasone and indomethacin, inhibitors of phospholipase A2 and cyclooxygenase, respectively, significantly inhibited prostaglandin E2 production at concentrations as low as 10(-8) and 10(-9) M but did not inhibit DNA synthesis. It is concluded (1) that prostaglandin E2 is the major arachidonic acid metabolite of rat tracheal epithelial cells, (2) that transformation does not significantly alter arachidonic acid metabolism in these cells, and (3) that neither prostaglandin E2 nor other arachidonic acid metabolites play a significant role in mitogenic stimulation of rat tracheal epithelial cells.
Duniec
Z M
ZM
Laboratory of Pulmonary Pathobiology, NIEHS, Research Triangle Park, NC 27709.
Eling
T E
TE
Jetten
A M
AM
Gray
T E
TE
Nettesheim
P
P
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014134:Tracheal Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D006133:Growth Substances; D011458:Prostaglandins E; D016718:Arachidonic Acid