Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways

• Published in: Molecular and cellular endocrinology Vol. 591; p. 112274
• Main Authors: Xiang, Yu, Liu, Shuangying, Wan, Shan, Chen, Qingqing, Song, Yang, Feng, Guofang, Zhang, Xinyue, Bai, Long, Zhu, Yimin
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.09.2024
• Subjects: Adult; Cells, Cultured; Female; Follicular Fluid - metabolism; Gene Expression Regulation - drug effects; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Human granulosa cell; Humans; Inflammation; Interleukin-1; Interleukin-1 - genetics; Interleukin-1 - metabolism; Interleukin-1alpha - genetics; Interleukin-1alpha - metabolism; Interleukin-1beta - metabolism; Luteal Cells - drug effects; Luteal Cells - metabolism; PCOS; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Receptors, Interleukin-1 Type I - genetics; Receptors, Interleukin-1 Type I - metabolism; SERPINE1; Signal Transduction; Human granulosa cell; Interleukin-1; PCOS; Inflammation; SERPINE1
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2024.112274

It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders. •The IL-1α and IL-1β levels are increased in follicular fluid from PCOS patients.•IL-1α and IL-1β induce primary human granulosa-lutein cell inflammatory response.•IL-1α and IL-1β upregulate SERPINE1 expression through IL-1R1-P50/P52 signaling pathways in human granulosa cells.