RRC ID 78285
著者 Wan S, Chen Q, Xiang Y, Sang Y, Tang M, Song Y, Feng G, Ye B, Bai L, Zhu Y.
タイトル 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.
ジャーナル Mol Cell Endocrinol
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.
巻・号 566-567
ページ 111891
公開日 2023-5-1
DOI 10.1016/j.mce.2023.111891
PII S0303-7207(23)00042-4
PMID 36801432
MeSH Cyclooxygenase 2 / genetics Cyclooxygenase 2 / metabolism Dinoprostone / metabolism Female Humans Luteal Cells* / metabolism Mitogen-Activated Protein Kinase 3 / metabolism NF-kappa B* / metabolism Signal Transduction
リソース情報
ヒト・動物細胞 KGN(RCB1154)