CYTOPLASMIC PHOSPHOLIPASE-A2 ACTIVITY AND GENE-EXPRESSION ARE STIMULATED BY TUMOR-NECROSIS-FACTOR - DEXAMETHASONE BLOCKS THE INDUCED SYNTHESIS
CYTOPLASMIC PHOSPHOLIPASE-A2 ACTIVITY AND GENE-EXPRESSION ARE STIMULATED BY TUMOR-NECROSIS-FACTOR - DEXAMETHASONE BLOCKS THE INDUCED SYNTHESIS
复制标题
DOI：
10.1073/pnas.90.10.4475
复制
发表时间：
1993-05-15
影响因子：
11.1
通讯作者：
HELLER, RA
中科院分区：
文献类型：
--
作者：
HOECK, WG;RAMESHA, CS;HELLER, RA
肿瘤坏死因子 a (TNF) 与其两个膜结合受体的相互作用启动了花生四烯酸及其衍生物参与的细胞内事件。在 HeLa 细胞中，TNF 处理可诱导花生四烯酸选择性、Ca2+ 依赖性细胞磷脂酶 A2 (cPLA2)。 TNF 本身会导致 cPLA2 活性适度增加，但与 Ca2+ 离子载体 A23187 一起提供强大的协同作用。在对 TNF 作出反应的几分钟内，cPLA2 就会磷酸化，并且在 Ca2+ 存在的情况下，其活性会增加 3 至 4 倍。 TNF 还会增加 cPLA2 mRNA 和蛋白质表达，估计在 8 小时内增加 5 倍。因此，cPLA2 活性的增加以双相时间依赖性方式发生。已知地塞米松可以拮抗 TNF 的作用，这里显示它可以抑制 TNF 诱导的基因表达并阻止 cPLA2 激活增加的第二阶段。我们的结果表明，cPLA2 激活可能提供调节功能，并可能解释 TNF 的促炎作用。
The interaction of tumor necrosis factor a (TNF) with its two membrane-bound receptors initiates intracellular events in which arachidonic acid and its derivatives are involved. In HeLa cells, TNF treatment induces an arachidonic acid-selective, Ca2+-dependent cellular phospholipase A2 (cPLA2). By itself, TNF causes a modest increase in cPLA2 activity, but with the Ca2+ ionophore A23187 it provides a strong synergistic action. Within minutes in response to TNF, cPLA2 becomes phosphorylated and in the presence of Ca2+ produces a 3- to 4-fold increase in activity. TNF also increases cPLA2 mRNA and protein expression, an estimated 5-fold increase in an 8-hr period. This increase in cPLA2 activity occurs, therefore, in a biphasic time-dependent manner. Dexamethasone, known to antagonize the action of TNF, is here shown to inhibit TNF-induced gene expression and to prevent the second phase of increase in cPLA2 activation. Our results suggest that the cPLA2 activation may provide a regulatory function and may explain the proinflammatory action of TNF.