Duniec Z M, Eling T E, Jetten A M, Gray T E, Nettesheim P
Laboratory of Pulmonary Pathobiology, NIEHS, Research Triangle Park, NC 27709.
Exp Lung Res. 1989 May;15(3):391-408. doi: 10.3109/01902148909087867.
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.
我们研究的目的是描绘培养的大鼠气管上皮细胞产生的花生四烯酸代谢物的概况，并确定这些细胞的转化是否会导致花生四烯酸代谢发生重大的定性或定量变化，以及花生四烯酸代谢物是否在大鼠气管细胞增殖的调节中发挥重要作用。我们的研究表明，前列腺素E2是正常和转化的大鼠气管上皮细胞产生的唯一主要类前列腺素。在用钙离子载体A23187、12-O-十四烷酰佛波醇-13-乙酸酯、花生四烯酸或血清刺激时，除前列腺素E2外，培养物还产生少量血栓素B2、前列腺素F2α和羟基二十碳四烯酸。有丝分裂原研究表明，所测试的肽生长因子均未刺激前列腺素E2的产生或DNA合成。另一方面，胎牛血清则能刺激两者。12-O-十四烷酰佛波醇-13-乙酸酯和花生四烯酸刺激了前列腺素E2的产生，但未导致DNA合成增加。地塞米松和吲哚美辛分别是磷脂酶A2和环氧化酶的抑制剂，在低至10^(-8)和10^(-9) M的浓度下就能显著抑制前列腺素E2的产生，但不抑制DNA合成。得出的结论是：(1)前列腺素E2是大鼠气管上皮细胞的主要花生四烯酸代谢物；(2)转化不会显著改变这些细胞中的花生四烯酸代谢；(3)前列腺素E2和其他花生四烯酸代谢物在大鼠气管上皮细胞的有丝分裂刺激中均不发挥重要作用。
