Masferrer J L, Reddy S T, Zweifel B S, Seibert K, Needleman P, Gilbert R S, Herschman H R
Department of Inflammatory Diseases Research, Searle T3G, St. Louis, Missouri.
J Pharmacol Exp Ther. 1994 Sep;270(3):1340-4.
Acute inflammatory stimuli elevate both the production of prostaglandins and the synthesis and activity of prostaglandin synthase/cyclooxygenase enzyme (COX) in murine peritoneal macrophages. Adrenalectomy also elevates prostaglandin production, COX synthesis and COX activity in these cells. We have utilized cDNA probes and antisera specific for the products of the prostaglandin synthase/cyclooxygenase-1 (COX-1) and TIS10/prostaglandin synthase-2/cyclooxygenase-2 (COX-2) genes to demonstrate that adrenalectomy causes elevation of mRNA and protein from the COX-2 gene, but not from the COX-1 gene, in peritoneal macrophages. Dexamethasone replacement suppressed the elevation of COX-2 mRNA message, COX-2 protein and the increased COX enzyme activity observed in adrenalectomized animals. In contrast, both COX-1 message and COX-1 protein levels were unaffected either by adrenalectomy or by dexamethasone administration. Thus, under normal physiological conditions, tonic glucocorticoid inhibition appears to play a major role in the in vivo regulation of the COX-2 gene. These data are consistent with COX-1 being the constitutive, housekeeping enzyme in macrophages in normal physiological conditions and with the enhanced prostaglandin synthesis seen after an inflammatory stimulus resulting from the rapid induction and activity of COX-2.
急性炎症刺激会提高小鼠腹膜巨噬细胞中前列腺素的生成以及前列腺素合酶/环氧化酶（COX）的合成与活性。肾上腺切除术也会提高这些细胞中前列腺素的生成、COX的合成及COX活性。我们利用针对前列腺素合酶/环氧化酶-1（COX-1）和TIS10/前列腺素合酶-2/环氧化酶-2（COX-2）基因产物的cDNA探针和抗血清，来证明肾上腺切除术会导致腹膜巨噬细胞中COX-2基因的mRNA和蛋白质水平升高，但不会导致COX-1基因的mRNA和蛋白质水平升高。地塞米松替代治疗抑制了肾上腺切除动物中观察到的COX-2 mRNA信息、COX-2蛋白质的升高以及COX酶活性的增加。相比之下，COX-1信息和COX-1蛋白质水平不受肾上腺切除术或地塞米松给药的影响。因此，在正常生理条件下，糖皮质激素的持续抑制似乎在COX-2基因的体内调节中起主要作用。这些数据与COX-1在正常生理条件下是巨噬细胞中的组成型管家酶以及炎症刺激后由于COX-2的快速诱导和活性而导致前列腺素合成增加相一致。
