Matsumoto H, Naraba H, Murakami M, Kudo I, Yamaki K, Ueno A, Oh-ishi S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
Biochem Biophys Res Commun. 1997 Jan 3;230(1):110-4. doi: 10.1006/bbrc.1996.5894.
Rat peritoneal macrophages were stimulated with lipopolysaccaride (LPS) for various periods and their ability to convert exogenous arachidonic acid to various prostanoids was examined. Unstimulated cells, which expressed cyclooxygenase (COX)-1 but not COX-2, produced thromboxane (TX) B2 > prostaglandin (PG) D2 > PGE2, whereas cells stimulated for 6-12 h with LPS exhibited marked increase in conversion to PGE2, which paralleled COX-2 induction, with minimal change in conversion to TXB2 and PGD2. Pharmacological studies showed that formation of PGE2 was mediated predominantly by COX-2, PGD2 by COX-1, and TXB2 by both COX-1 and COX-2 depending upon the timing of LPS stimulation. Measurement of the conversion of exogenous PGH2 to each prostanoid in cell lysates demonstrated LPS-dependent increase in PGE2 synthase activity that was degenerated by pretreatment with actinomycin D or cycloheximide. Thus, concordant induction of terminal PGE2 synthase with COX-2 leads to the preferred production of PGE2 to TXB2 and PGD2 by LPS-stimulated macrophages.
用脂多糖（LPS）刺激大鼠腹膜巨噬细胞不同时间，检测其将外源性花生四烯酸转化为各种前列腺素的能力。未受刺激的细胞表达环氧化酶（COX）-1但不表达COX-2，产生血栓素（TX）B2 > 前列腺素（PG）D2 > PGE2，而用LPS刺激6 - 12小时的细胞，PGE2转化显著增加，这与COX-2诱导平行，TXB2和PGD2转化变化最小。药理学研究表明，PGE2的形成主要由COX-2介导，PGD2由COX-1介导，TXB2由COX-1和COX-2共同介导，这取决于LPS刺激的时间。在细胞裂解物中测量外源性PGH2向每种前列腺素的转化，结果表明LPS依赖性增加的PGE2合酶活性可被放线菌素D或环己酰亚胺预处理所降解。因此，COX-2与终末PGE2合酶的协同诱导导致LPS刺激的巨噬细胞优先产生PGE2而非TXB2和PGD2。
