Kuiper J, Kamps J A, Van Berkel T J
Division of Biopharmaceutics, University of Leiden, The Netherlands.
J Biol Chem. 1989 Apr 25;264(12):6874-8.
Administration of phorbol 12-myristate 13-acetate (PMA) to rats in vivo resulted in the induction of ornithine decarboxylase activity in the liver which could be blocked by preinjection of indomethacin, a cyclooxygenase inhibitor. In vitro administration of PMA to primary cultures of rat parenchymal cells did not lead to an induction of ornithine decarboxylase activity. It was investigated to what extent non-parenchymal liver cells could play an intermediary role in the expression of the PMA effect on ornithine decarboxylase activity in parenchymal liver cells. Addition of conditioned medium from PMA-activated Kupffer cells to cultured parenchymal cells led to the induction of ornithine decarboxylase activity in parenchymal cells. This effect was not observed with conditioned medium from untreated Kupffer cells or from Kupffer cells treated with PMA plus indomethacin. Conditioned media from PMA-treated or untreated endothelial liver cells were ineffective in the induction of ornithine decarboxylase activity in parenchymal liver cells. Prostaglandin D2, the main eicosanoid produced by Kupffer cells, was able to stimulate the synthesis of ornithine decarboxylase in parenchymal liver cells (up to 40-fold) in a dose-dependent way. Prostaglandin (PG) D2 appeared to be a more potent inducer of ornithine decarboxylase activity in parenchymal cells than PGE1 and PGE2. It is concluded that intercellular communication inside the liver mediated by prostaglandins derived from activated Kupffer cells may form a mechanism to induce synthesis of specific proteins in parenchymal cells.
给大鼠体内注射佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）可诱导肝脏中鸟氨酸脱羧酶活性，而预先注射环氧化酶抑制剂吲哚美辛可阻断这种诱导作用。在体外，将PMA应用于大鼠实质细胞原代培养物中不会导致鸟氨酸脱羧酶活性的诱导。研究了非实质肝细胞在PMA对实质肝细胞中鸟氨酸脱羧酶活性的影响表达中能起到多大程度的中介作用。将来自PMA激活的库普弗细胞的条件培养基添加到培养的实质细胞中会导致实质细胞中鸟氨酸脱羧酶活性的诱导。用未处理的库普弗细胞或用PMA加吲哚美辛处理的库普弗细胞的条件培养基未观察到这种效应。来自PMA处理或未处理的肝内皮细胞的条件培养基在诱导实质肝细胞中鸟氨酸脱羧酶活性方面无效。前列腺素D2是库普弗细胞产生的主要类花生酸，它能够以剂量依赖的方式刺激实质肝细胞中鸟氨酸脱羧酶的合成（高达40倍）。前列腺素（PG）D2似乎比PGE1和PGE2更有效地诱导实质细胞中鸟氨酸脱羧酶活性。结论是，由活化的库普弗细胞衍生的前列腺素介导的肝脏内细胞间通讯可能形成一种机制，以诱导实质细胞中特定蛋白质的合成。
