Arachidonic Acid Metabolism in Normal and Transformed Rat Tracheal Epithelial Cells and its Possible Role in the Regulation of Cell Proliferation

Abstract

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 B^ prostaglandin F_2α and hydroxyeicosate-traenoic acidfs) 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. 12-0-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.