C/EBP-β and SIRT1 regulate IL-18 expression in the proliferative phase endometria of polycystic ovary syndrome patients

Abstract

Background: Previous studies have shown that polycystic ovary syndrome (PCOS) patients suffer from low-grade chronic inflammation. Furthermore, our previous studies have confirmed that IL-18 is highly expressed in the serum and endometria of PCOS patients. Nevertheless, the mechanisms underlying IL-18 elevation remain unclear. This study aims to explore the signaling pathways that lead to IL-18 upregulation in the endometria of PCOS patients. Methods: Using the TF-Search tool, we predicted that C/EBP-β may be a transcription factor for IL-18 and that deacetylase SIRT1 could be involved in its regulation. Subsequently, we analyzed SIRT1 and C/EBP-β in the proliferative endometria of PCOS patients and healthy control using immunohistochemistry, real-time quantitative PCR and western blot; PCOS diagnosis was based on the 2003 Rotterdam ESHRE/ASRM criteria. We further verified the interaction between C/EBP-β and IL-18 using a double luciferase assay. Results: SIRT1 and C/EBP-β gene and protein levels in the proliferative endometria of PCOS patients were significantly higher than the control group. Immunohistochemical experiments confirmed that SIRT1 was primarily expressed in the endometrial nucleus, while C/EBP-β was predominantly expressed in the endometrial nucleus and cytoplasm. Double luciferase assay verified the interaction between C/EBP-β and IL-18. Conclusion: SIRT1 and C/EBP-β are probable IL-18 regulatory mechanism in the endometria of PCOS patients.