1. Academic Validation
  2. Interleukin-1 increases cyclooxygenase-2 expression and prostaglandin E2 production in human granulosa-lutein cell via nuclear factor kappa B/P65 and extracellular signal-regulated kinase 1/2 signaling pathways

Interleukin-1 increases cyclooxygenase-2 expression and prostaglandin E2 production in human granulosa-lutein cell via nuclear factor kappa B/P65 and extracellular signal-regulated kinase 1/2 signaling pathways

  • Mol Cell Endocrinol. 2023 Feb 17;111891. doi: 10.1016/j.mce.2023.111891.
Shan Wan 1 Qingqing Chen 1 Yu Xiang 1 Yimiao Sang 1 Minyue Tang 1 Yang Song 1 Guofang Feng 1 Bingru Ye 1 Long Bai 2 Yimin Zhu 3
Affiliations

Affiliations

  • 1 Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310002, China; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310002, China.
  • 2 Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310002, China; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310002, China. Electronic address: bailong0375@zju.edu.cn.
  • 3 Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310002, China; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310002, China. Electronic address: zhuyim@zju.edu.cn.
Abstract

A multitude of cytokines have been reported to participate in the folliculogenesis process in female. Interleukin-1 (IL-1), belonging to interleukin family, is originally identified as an important immune factor involved in inflammation response. Besides the immunity system, IL-1 is also expressed in reproductive system. However, the role of IL-1 in regulating ovarian follicle function remains to be elucidated. In the current study, using the primary human granulosa-lutein (hGL) and immortalized human granulosa-like tumor cell line (KGN) models, we demonstrated that both IL-1α and IL-1β increased prostaglandin E2 (PGE2) production via upregulating its cyclooxygenase (COX) Enzyme COX-2 expression in human granulosa cells. Mechanistically, IL-1α and IL-1β treatment activated nuclear factor kappa B (NF-κB) signaling pathway. Using the specific siRNA to knock down endogenous gene expression, we found that the inhibition of p65 expression abolished IL-1α and IL-1β-induced upregulation of COX-2 expression whereas knockdown of p50 and p52 had no effect. Moreover, our results also showed that IL-1α and IL-1β promoted the nuclear translocation of p65. ChIP assay demonstrated the transcriptional regulation of p65 on COX-2 expression. Additionally, we also found that IL-1α and IL-1β could activate the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. The inhibition of ERK1/2 signaling pathway activation reversed IL-1α and IL-1β-induced upregulation of COX-2 expression. Our findings shed LIGHT on the cellular and molecular mechanisms by which IL-1 modulates the COX-2 expression through NF-κB/P65 and ERK1/2 signaling pathways in human granulosa cells.

Keywords

COX-2; ERK1/2; Human granulosa cell; Interleukin-1; P65.

Figures
Products