CDNA CLONING AND FUNCTIONAL-ACTIVITY OF A GLUCOCORTICOID-REGULATED INFLAMMATORY CYCLOOXYGENASE
CDNA CLONING AND FUNCTIONAL-ACTIVITY OF A GLUCOCORTICOID-REGULATED INFLAMMATORY CYCLOOXYGENASE
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DOI：
10.1073/pnas.89.11.4888
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发表时间：
1992-06-01
影响因子：
11.1
通讯作者：
YOUNG, DA
中科院分区：
文献类型：
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作者：
OBANION, MK;WINN, VD;YOUNG, DA
糖皮质激素是环氧合酶的有效抑制剂，环氧合酶是前列腺素合成的关键调节剂;然而，其发生机制尚未完全了解。我们已经克隆了一个4.1-脱氢酶（kb）的cDNA，不同于以前克隆的环氧合酶（2.8 kb），赋予环氧合酶活性转染细胞。这种新发现的环氧合酶的mRNA是独特的，因为它的长3'非翻译区含有许多AUUUA重复。在小鼠成纤维细胞和人单核细胞中，血清或白细胞介素1-β分别使4.1-kb环氧合酶mRNA水平迅速升高，糖皮质激素使其降低，而2.8-kb环氧合酶mRNA水平不变。在放线菌酮的存在下观察到类似的效果，其中4.1-kb，但不是2.8-kb，mRNA被大大超诱导。因此，存在组成型（2.8 kb）和调节型（4.1 kb）环氧合酶种类，后者最有可能是炎症的主要介质。
The antiinflammatory glucocorticoids are potent inhibitors of cyclooxygenase, a key regulator of prostaglandin synthesis; yet, the mechanism(s) by which this occurs is not fully understood. We have cloned a 4.1-kilobase (kb) cDNA, distinct from the previously cloned cyclooxygenase (2.8 kb), that confers cyclooxygenase activity to transfected cells. The mRNA for this newly discovered cyclooxygenase is unique for its long 3' untranslated region containing many AUUUA repeats. Levels of the 4.1-kb cyclooxygenase mRNA are rapidly increased by serum or interleukin 1-beta in mouse fibroblasts and human monocytes, respectively, and decreased by glucocorticoids, whereas levels of the 2.8-kb cyclooxygenase mRNA do not change. Similar effects are seen in the presence of cycloheximide where the 4.1-kb, but not the 2.8-kb, mRNA is greatly superinduced. Thus, there are both constitutive (2.8 kb) and regulated (4.1 kb) cyclooxygenase species, the latter most likely being a major mediator of inflammation.