Tong Min, Tai Hsin-Hsiung
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Arch Biochem Biophys. 2005 Mar 1;435(1):50-5. doi: 10.1016/j.abb.2004.11.031.
Dexamethasone induced the expression of 15-PGDH in a time- and concentration-dependent manner in A549 human lung adenocarcinoma cells. Maximal induction was observed at 10nM. Induction of 15-PGDH expression was also achieved by other synthetic glucocorticoids. Induction was inhibited by the addition of pro-inflammatory cytokines and phorbol ester. These pro-inflammatory agents were also shown to induce COX-2 expression. PMA was found to be the most effective stimulator of COX-2 expression and the most potent inhibitor of dexamethasone-induced 15-PGDH expression. Attenuation of dexamethasone-induced 15-PGDH expression by PMA was, in part, due to a protein kinase C-mediated mechanism. The induction of 15-PGDH expression by dexamethasone was blocked by a glucocorticoid receptor antagonist RU 486 and by a nuclear translocation inhibitor geldanamycin, indicating that the induction is a genetic mechanism. The induction of 15-PGDH expression by dexamethasone and other glucocorticoids at the therapeutic level provides an additional biochemical mechanism for the anti-inflammatory action of these glucocorticoids.
地塞米松在A549人肺腺癌细胞中以时间和浓度依赖性方式诱导15-前列腺素脱氢酶（15-PGDH）的表达。在10nM时观察到最大诱导作用。其他合成糖皮质激素也能诱导15-PGDH表达。添加促炎细胞因子和佛波酯可抑制诱导作用。这些促炎剂还被证明可诱导环氧化酶-2（COX-2）表达。发现佛波酯肉豆蔻酸酯（PMA）是COX-2表达最有效的刺激剂，也是地塞米松诱导的15-PGDH表达最有效的抑制剂。PMA对地塞米松诱导的15-PGDH表达的减弱部分归因于蛋白激酶C介导的机制。地塞米松诱导的15-PGDH表达被糖皮质激素受体拮抗剂RU 486和核转位抑制剂格尔德霉素阻断，表明该诱导是一种遗传机制。地塞米松和其他糖皮质激素在治疗水平上诱导15-PGDH表达为这些糖皮质激素的抗炎作用提供了一种额外的生化机制。
