Inase N, Levine T M, Lazarus S C
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Am J Respir Cell Mol Biol. 1993 Nov;9(5):526-32. doi: 10.1165/ajrcmb/9.5.526.
A mitogen-inducible prostaglandin G/H synthase (PGHS-2 or cyclooxygenase-2) has recently been cloned from chicken and mouse fibroblasts. This protein is distinct from classic prostaglandin G/H synthase (PGHS-1 or cyclooxygenase-1) but has a similar enzymatic activity. Because PGHS-1 is a rate-limiting enzyme in the synthesis of prostaglandins, PGHS-2 may also play an important role in prostaglandin production. To examine whether PGHS-2 is induced by phorbol ester in mast cells, we studied mRNA expression of PGHS-2 and also measured prostaglandin D2 (PGD2) production when canine mastocytoma cells were incubated with phorbol myristate acetate (PMA). PGHS-2 mRNA was induced by PMA, with a maximal induction after 4 h of incubation with 10 nM PMA. There was concentration-dependent production of PGD2 after incubation with PMA. In contrast, PGHS-1 mRNA was expressed in resting cells, and the expression of PGHS-1 mRNA was down-regulated by PMA. Dexamethasone inhibited PMA-induced mRNA expression of PGHS-2 and PGD2 production. Aspirin had no effect on mRNA expression of PGHS-2 but inhibited PGD2 production. In conclusion, PGHS-2 is induced by phorbol ester in canine mast cells. We speculate that PGHS-2 may be important in airway inflammation in which mast cells are activated.
一种丝裂原诱导型前列腺素G/H合酶(PGHS-2或环氧化酶-2)最近已从鸡和小鼠成纤维细胞中克隆出来。这种蛋白质与经典的前列腺素G/H合酶(PGHS-1或环氧化酶-1)不同,但具有相似的酶活性。由于PGHS-1是前列腺素合成中的限速酶,PGHS-2可能在前列腺素的产生中也起重要作用。为了研究PGHS-2是否在肥大细胞中被佛波酯诱导,我们研究了PGHS-2的mRNA表达,并在犬肥大细胞瘤细胞与佛波酯肉豆蔻酸乙酸酯(PMA)孵育时测量了前列腺素D2(PGD2)的产生。PGHS-2 mRNA被PMA诱导,在用10 nM PMA孵育4小时后诱导达到最大值。与PMA孵育后PGD2的产生呈浓度依赖性。相反,PGHS-1 mRNA在静息细胞中表达,并且PGHS-1 mRNA的表达被PMA下调。地塞米松抑制PMA诱导的PGHS-2 mRNA表达和PGD2产生。阿司匹林对PGHS-2的mRNA表达没有影响,但抑制PGD2的产生。总之,PGHS-2在犬肥大细胞中被佛波酯诱导。我们推测PGHS-2在肥大细胞被激活的气道炎症中可能很重要。