Glucocorticoids stimulate prostaglandin H synthase type-2 (PGHS-2) in the fibroblast cells in human amnion cultures

Glucocorticoids stimulate prostaglandin H synthase type-2 (PGHS-2) in the fibroblast cells in human amnion cultures
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DOI:
10.1016/0303-7207(95)03739-x
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发表时间:
1996-03-25
影响因子:
4.1
通讯作者:
Gibb, W
Gibb, W
中科院分区:
医学2区
文献类型:
--
作者:
Economopoulos, P;Sun, M;Gibb, W

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人羊膜可能是参与分娩开始的胎盘素的重要来源。糖皮质激素可能是羊膜前列腺素合成的调节剂,并已显示刺激原代单层培养的人羊膜细胞的PGE(2)输出和前列腺素H-2合酶(PGHS)活性。存在两种已知的PGHS同种型:组成型表达的PGHS-1和诱导型PGHS-2。最近的研究表明,后一种亚型是由糖皮质激素诱导的。羊膜由单层上皮细胞组成,其下是含有成纤维细胞的间充质层,并且不知道哪些细胞类型以这种方式对糖皮质激素产生反应。在本研究中,我们证明,虽然这两种细胞类型都存在于培养中,PGHS-2蛋白和mRNA水平增加专门在成纤维细胞内响应地塞米松,而PGHS-1蛋白和mRNA水平保持在两种细胞类型的不受影响。这些结果表明,糖皮质激素刺激培养的羊膜细胞中的PGE(2)是由于成纤维细胞中PGHS-2基因转录的上调,这些以前被忽视的细胞可能在参与分娩的前列腺素合成中发挥重要作用。
The human amnion may be an important source of prostaglandins involved in the onset of labour. Glucocorticoids are possible regulators of amnion prostaglandin synthesis and have been shown to stimulate the PGE(2) output and prostaglandin H-2 synthase (PGHS) activity of human amnion cells maintained in primary monolayer culture. There are two known isoforms of PGHS: the constitutively expressed PGHS-1 and the inducible PGHS-2. Recent studies have shown that the latter isoform is induced by glucocorticoids The amnion consists of a single layer of epithelial cells beneath which lies a mesenchymal layer containing fibroblasts and it is not known which cell types are responding to glucocorticoids in this manner. In the present study, we demonstrate that although both cell types are present in culture, PGHS-2 protein and mRNA levels increase exclusively within the fibroblasts in response to dexamethasone, while PGHS-1 protein and mRNA levels remain unaffected in both cell types. These results suggest that the stimulation of PGE(2) in cultured amnion cells by glucocorticoids is due to an upregulation of PGHS-2 gene transcription in fibroblasts, and that these previously overlooked cells may have important roles to play in the synthesis of prostaglandins involved in labour.