Paradoxical Induction of ALOX15/15B by Cortisol in Human Amnion Fibroblasts: Implications for Inflammatory Responses of the Fetal Membranes at Parturition.
Paradoxical Induction of ALOX15/15B by Cortisol in Human Amnion Fibroblasts: Implications for Inflammatory Responses of the Fetal Membranes at Parturition.
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DOI：
10.3390/ijms241310881
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发表时间：
2023-06-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
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胎膜炎症是分娩中不可或缺的事件，前列腺素E2（PGE 2）合成的增加是引发临产的最终产物之一。除了PGE 2，胎膜还具有很大的皮质醇再生能力。有趣的是，在分娩时胎膜中经典抗炎糖皮质激素的量增加的情况下，如何实现PGE 2合成的增加。由脂氧合酶15/15 B（ALOX 15/15 B）合成的15（S）-羟基二十碳四烯酸（15（S）-HETE）已显示出增强羊膜成纤维细胞中炎症诱导的PGE 2合成。在此，我们检测了糖皮质激素是否可以诱导ALOX 15/15 B表达和15（S）-HETE产生，以促进分娩时羊膜成纤维细胞中PGE 2的合成。我们发现，皮质醇和15（S）-HETE丰度增加羊膜在分娩。皮质醇在羊膜成纤维细胞中矛盾地诱导ALOX 15/15 B表达和15（S）-HETE产生。机制研究表明，这种矛盾的诱导作用是由p300介导的组蛋白乙酰化和糖皮质激素受体与转录因子CREB和STAT 3的相互作用介导的。总之，在胎膜中再生的皮质醇可以矛盾地诱导人羊膜成纤维细胞中的ALOX 15/15 B表达和15（S）-HETE产生，这可能进一步有助于在用于分娩的胎膜的炎症反应中诱导PGE 2合成。
Inflammation of the fetal membranes is an indispensable event of parturition, with increasing prostaglandin E2 (PGE2) synthesis as one of the ultimate products that prime labor onset. In addition to PGE2, the fetal membranes also boast a large capacity for cortisol regeneration. It is intriguing how increased PGE2 synthesis is achieved in the presence of increasing amounts of classical anti-inflammatory glucocorticoids in the fetal membranes at parturition. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) synthesized by lipoxygenase 15/15B (ALOX15/15B) has been shown to enhance inflammation-induced PGE2 synthesis in amnion fibroblasts. Here, we examined whether glucocorticoids could induce ALOX15/15B expression and 15(S)-HETE production to promote PGE2 synthesis in amnion fibroblasts at parturition. We found that cortisol and 15(S)-HETE abundance increased parallelly in the amnion at parturition. Cortisol induced ALOX15/15B expression and 15(S)-HETE production paradoxically in amnion fibroblasts. Mechanism study revealed that this paradoxical induction was mediated by p300-mediated histone acetylation and interaction of glucocorticoid receptor with transcription factors CREB and STAT3. Conclusively, cortisol regenerated in the fetal membranes can paradoxically induce ALOX15/15B expression and 15(S)-HETE production in human amnion fibroblasts, which may further assist in the induction of PGE2 synthesis in the inflammatory responses of the fetal membranes for parturition.
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影响因子：
4.1
作者：
Economopoulos, P;Sun, M;Gibb, W
通讯作者：
Gibb, W
人羊膜成纤维细胞中血清淀粉样蛋白 A1 诱导促炎基因
影响因子：
4.6
作者：
Li W;Wang W;Zuo R;Liu C;Shu Q;Ying H;Sun K
通讯作者：
Sun K
影响因子：
14.9
作者：
Beato, M;Eisfeld, K
通讯作者：
Eisfeld, K
影响因子：
15.9
作者：
CASEY, ML;MACDONALD, PC;MITCHELL, MD
通讯作者：
MITCHELL, MD
DOI：
10.1073/pnas.90.10.4475
发表时间：
1993-05-15
影响因子：
11.1
作者：
HOECK, WG;RAMESHA, CS;HELLER, RA
通讯作者：
HELLER, RA