Cross-talk between cyclooxygenase and nitric oxide pathways: prostaglandin E2 negatively modulates induction of nitric oxide synthase by interleukin 1.
Cross-talk between cyclooxygenase and nitric oxide pathways: prostaglandin E2 negatively modulates induction of nitric oxide synthase by interleukin 1.
复制标题
环氧合酶和一氧化氮途径之间的串扰：前列腺素 E2 负向调节白细胞介素 1 对一氧化氮合酶的诱导。
DOI：
10.1073/pnas.91.25.12168
复制
发表时间：
1994
影响因子：
11.1
通讯作者：
Aubrey R. Morrison
中科院分区：
文献类型：
--
作者：
T. Tetsuka;D. Daphna;S. Srivastava;L. D. Baier;J. Dumaine;Aubrey R. Morrison
炎性细胞因子白细胞介素 1 β (IL-1 β) 诱导环氧合酶 (COX) 和一氧化氮合酶 (NOS)，同时系膜细胞释放前列腺素 (PG) 和一氧化氮 (NO) 增加。最近，已经描述了NO对COX酶的激活。然而，COX产物（PGs）对NO途径的影响尚未完全阐明。因此，我们确定了 COX 抑制和外源 PG 对大鼠系膜细胞 NO 产生和 NOS 诱导的影响。 COX 抑制剂吲哚美辛可增强 IL-1 β 诱导的诱导型一氧化氮合酶 (iNOS) mRNA 的稳态水平和亚硝酸盐的产生。通过用外源性 PGE2 替代内源性 PGE2，吲哚美辛的作用呈剂量依赖性逆转，外源性 PGE2 是大鼠系膜细胞中 COX 途径的主要产物。与 PGE2 相比，PGI2 的稳定类似物 carba 前列环素可增强 IL-1 β 诱导的 iNOS mRNA 水平和亚硝酸盐的产生。 Forskolin 是一种腺苷酸环化酶激活剂，可模仿 carba 前列环素的作用，但不模仿 PGE2。这些数据表明（i）内源性PGE2下调iNOS诱导，（ii）PGE2对iNOS诱导的这种抑制作用不是由腺苷酸环化酶的激活介导的，以及（iii）外源性PGI2可能通过腺苷酸环化酶的激活来刺激COX诱导。
The inflammatory cytokine interleukin 1 beta (IL-1 beta) induces both cyclooxygenase (COX) and nitric oxide synthase (NOS) with increases in the release of prostaglandin (PG) and nitric oxide (NO) by mesangial cells. Recently, activation of the COX enzyme by NO has been described. However, the effects of COX products (PGs) on the NO pathway have not been fully clarified. Thus we determined the effect of COX inhibition and exogenous PGs on NO production and NOS induction in rat mesangial cells. A COX inhibitor, indomethacin, enhanced IL-1 beta-induced steady-state level of the inducible NOS (iNOS) mRNA and nitrite production. The effect of indomethacin was dose dependently reversed by the replacement of endogenous PGE2 with exogenous PGE2, which is the predominant product of the COX pathway in rat mesangial cells. In contrast to PGE2, a stable analog of PGI2, carba prostacyclin, enhanced IL-1 beta-induced iNOS mRNA levels and nitrite production. Forskolin, an activator of the adenylate cyclase, mimicked the effect of carba prostacyclin but not PGE2. These data suggest that (i) endogenous PGE2 downregulates iNOS induction, (ii) this inhibitory effect of PGE2 on iNOS induction is not mediated by activation of adenylate cyclase, and (iii) exogenous PGI2 stimulates COX induction possibly by activation of adenylate cyclase.