17 beta-estradiol increases inducible nitric oxide synthase expression in macrophages.
17 beta-estradiol increases inducible nitric oxide synthase expression in macrophages.
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DOI：
10.1016/s0006-291x(03)00477-7
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发表时间：
2003-04
影响因子：
3.1
通讯作者：
H. You;Ji Young Kim;H. Jeong
中科院分区：
文献类型：
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作者：
H. You;Ji Young Kim;H. Jeong
在某些组织中，已知17β-雌二醇（E2）可增加内皮NOS表达。本研究观察了E2对大鼠腹腔巨噬细胞雌激素受体（ERα和ER β）和诱导型一氧化氮合酶（iNOS）表达的影响，并分析了其作用机制。逆转录聚合酶链反应（RT-PCR）和瞬时转染实验表明，腹腔巨噬细胞对E2有反应，同时表达ERα和ERβ mRNA。与E2孵育导致ERβ mRNA表达增加。当大鼠腹腔巨噬细胞与生理浓度的E2孵育时，E2诱导NO产生的剂量依赖性增加。E2在浓度超过10− 11 M时会显著影响分泌，其最大效应出现在10− 8 M的浓度。RT-PCR反应显示，NO分泌的增加是由于iNOS mRNA的增加。与雌激素受体拮抗剂ICI 182.780共孵育，抑制E2对NO产生和iNOS表达的影响。因此，E2刺激iNOS表达的经典受体介导的途径。我们在此证明，E2增加巨噬细胞中iNOS的表达，这种作用似乎是ER激活的结果。
In some tissues 17β-estradiol (E2) is known to increase endothelial NOS expression. In the present study we examined the effects of E2 on estrogen receptors (ERα and β) and inducible nitric oxide synthase (iNOS) expression and analyzed the mechanisms in rat peritoneal macrophages. Reverse-transcription polymerase chain (RT-PCR) and transient transfection experiments using a reporter plasmid that contained a luciferase gene under the transcriptional control of an estrogen-responsive elements revealed that peritoneal macrophages are responsive to E2 and express both ERα and ERβ mRNAs. Incubation with E2 leads to an increased ERβ mRNA expression. When rat peritoneal macrophages were incubated with physiological concentrations of E2, E2 induced a dose-dependent increase in NO production. E2 significantly affected secretion at concentration levels of more than 10−11M, and its maximum effect was at a concentration of 10−8M. RT-PCR reactions showed that increases in NO secretion were due to an increase in iNOS mRNA. Coincubation with ICI 182.780, an estrogen-receptor antagonist, inhibited the influence of E2 on NO production and iNOS expression. Thus E2 stimulated iNOS expression by a classic receptor-mediated pathway. We hereby prove that E2 increases the iNOS expression in macrophages and this effect appears to be the consequence of ER activation.