Translator Disclaimer
1 January 2008 Paradox of Glucocorticoid-Induced Cytosolic Phospholipase A2 Group IVA Messenger RNA Expression Involves Glucocorticoid Receptor Binding to the Promoter in Human Amnion Fibroblasts
Chunming Guo, Zhen Yang, Wenjiao Li, Ping Zhu, Leslie Myatt, Kang Sun
Author Affiliations +
Abstract

Glucocorticoids (GCs) are well-known anti-inflammatory drugs inhibiting prostaglandin production. Paradoxically, GCs are reported to stimulate cytosolic phosphoplipase A2 group IVA (PLA2G4A) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in human amnion fibroblasts. This study was designed to examine the molecular mechanisms underlying glucocorticoid-induced PLA2G4A expression in human amnion fibroblasts. Our data showed that cortisol (0.01∼1 μM) increased PLA2G4A mRNA level in a dose-dependent manner in human amnion fibroblasts, which was blocked by glucocorticoid receptor antagonist RU486 (1 μM) as well as by the mRNA transcription inhibitor 5,6-dichlorobenzimidazole riboside (DRB; 75 μM). Concurrently, cortisol (0.01∼1 μM) decreased rather than increased proinflammatory cytokine mRNA levels, including interleukin 1 beta (IL1B), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF), in a dose-dependent manner in human amnion fibroblasts. Chromatin immunoprecipitation assay revealed that glucocorticoid receptor was bound to PLA2G4A promoter in human amnion fibroblasts upon cortisol stimulation. This was confirmed by electrophoretic mobility shift assay showing that nuclear protein extracted from human amnion fibroblasts upon cortisol stimulation could bind the synthesized oligonucleotide sequence corresponding to PLA2G4A promoter region from −95 bp to −65 bp bearing the putative glucocorticoid response element. This binding was super shifted by glucocorticoid receptor antibody. In conclusion, we demonstrated in this study that cortisol increased PLA2G4A mRNA level via GR-dependent ongoing transcription in human amnion fibroblasts by activating the binding of GR to PLA2G4A promoter directly, and this effect appeared unlikely to be secondary to the effect of cortisol on the expression of proinflammatory cytokines in human amnion fibroblasts.

Chunming Guo, Zhen Yang, Wenjiao Li, Ping Zhu, Leslie Myatt, and Kang Sun "Paradox of Glucocorticoid-Induced Cytosolic Phospholipase A2 Group IVA Messenger RNA Expression Involves Glucocorticoid Receptor Binding to the Promoter in Human Amnion Fibroblasts," Biology of Reproduction 78(1), 193-197, (1 January 2008). https://doi.org/10.1095/biolreprod.107.063990
Received: 5 July 2007; Accepted: 1 September 2007; Published: 1 January 2008
JOURNAL ARTICLE
5 PAGES


Share
SHARE
KEYWORDS
amnion
Cortisol
glucocorticoid receptor
parturition
PLA2G4A
placenta
pregnancy
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top