Involvement of STAT3 in the synergistic induction of 11β‐HSD1 by SAA1 and cortisol in human amnion fibroblasts

• Published in: American journal of reproductive immunology (1989) 2019-08, Vol.82 (2), p.e13150-n/a
• Main Authors: Lu, Yi, Zhou, Qiong, Lu, Jiang‐Wen, Wang, Wang‐Sheng, Sun, Kang
• Format: Article
• Language: English
• Subjects: Amnion; Amyloid; Cortisol; fetal membranes; Fetuses; Fibroblasts; glucocorticoids; Hormones; inflammation; Parturition; Phosphorylation; preterm; serum amyloid A1; siRNA; Stat3 protein
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.13150

Problem Cortisol, which is regenerated from biologically inactive cortisone by 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) in human fetal membranes, may play an important role in human parturition. Recently, we have demonstrated that human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute‐phase protein of inflammation, and SAA1 may be engaged in multiple actions associated with human parturition. It remains to be determined whether SAA1 can interact with cortisol in the regulation of 11β‐HSD1 in the fetal membranes. Method of Study In the current study, we examined the regulation of 11β‐HSD1 expression by SAA1, and the interaction between SAA1 and cortisol in the regulation of 11β‐HSD1 expression in primary human amnion fibroblasts and amnion tissue. Results Either SAA1 or cortisol induced 11β‐HSD1 expression in a concentration‐dependent manner. Combination of SAA1 and cortisol synergistically enhanced 11β‐HSD1 expression. Mechanism studies revealed that SAA1 and cortisol induced the phosphorylation of the transcription factor STAT3 in a sequential order with the induction by SAA1 preceding the induction by cortisol. Furthermore, the induction of 11β‐HSD1 expression by either SAA1 or cortisol or combination of SAA1 and cortisol was blocked by STAT3 inhibition with its antagonist S3I‐201 or siRNA‐mediated knockdown. Conclusion This study has demonstrated that SAA1 and cortisol can reinforce each other in the induction of 11β‐HSD1 expression through sequential phosphorylation of STAT3. The synergistic enhancement of 11β‐HSD1 expression by SAA1 and cortisol may lead to excessive cortisol accumulation in the fetal membranes at parturition.