C/EBP-β and SIRT1 regulate IL-18 expression in the proliferative phase endometrium of patients with polycystic ovary syndrome (PCOS)

Abstract Background：Previous studies have shown that patients with polycystic ovary syndrome (PCOS) tend to suffer from low-grade chronic inflammation. Besides, our previous studies have confirmed that IL-18 is highly expressed in the serum and endometrium of patients with PCOS. Nevertheless, the mechanism underlying IL-18 elevation remains unclear. The aim of this study was to explore the signaling pathways that lead to the up-regulation of IL-18 in the endometrium of PCOS patients. Materials and Methods: By using the TF-Search tool, we predicted that C/EBP-β might be a transcription factor of IL-18, and deacetylase SIRT1 might be involved in its regulation. Consequently, SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients and control groups were analyzed using immunohistochemistry, real-time quantitative PCR and Western Blot; the diagnosis of PCOS was based on the 2003 Rotterdam ESHRE/ASRM criteria. The interaction between C/EBP-β and IL-18 was verified by double luciferase assay. Results: The gene and protein levels of SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients were significantly higher compared to the control group. Immunohistochemical experiments confirmed that SIRT1 was mainly expressed in the endometrial nucleus, while C/EBP-β was mainly expressed in the endometrial nucleus and cytoplasm. The interaction between C/EBP-β and IL-18 was confirmed by double luciferase assay. Conclusion: SIRT1 and C/EBP-β are highly expressed in the endometrium of PCOS patients, and may participate in the regulation of IL-18. These results further our understanding of the role of C/EBP-β in PCOS and may be used as a basis for the development of targeted therapies for this disease.