IL1α and IL4 signalling in human ovarian surface epithelial cells

Georgia Papacleovoulou, Hilary O D Critchley, Stephen G Hillier, J Ian Mason

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


The human ovarian surface epithelium (hOSE) is a mesothelial layer that surrounds the ovary and undergoes injury and repair cycles after ovulation-associated inflammation. We previously showed that IL4 is a key regulator of progesterone bioavailability during post-ovulatory hOSE repair as it differentially up-regulated 3β-HSD1 and 3β-HSD2 mRNA transcripts and total 3β-hydroxysteroid dehydrogenase activity whereas it inhibited androgen receptor (AR) expression. We now show that the pro-inflammatory effect of IL1α on 3β-HSD1 expression is mediated by nuclear factor-κB (NF-κB), whereas its anti-inflammatory action on 3β-HSD2 expression is exerted via p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and NF-κB signalling pathways. The anti-inflammatory IL4 effects on 3β-HSD1 and 3β-HSD2 mRNA expression are mediated through STAT6 and PI3K signalling networks. IL4 effects on AR and 3β-HSD2 expression involve the p38 MAPK pathway. We also document that IL4 up-regulates lysyl oxidase (LOX) mRNA transcripts, a key gene for extracellular matrix (ECM) deposition and inhibits IL1α-induced expression of cyclooxygenase-2 (COX-2) mRNA, a gene involved in breakdown of ECM, showing a further role in post-ovulatory wound healing. We conclude that IL1α and IL4 actions in the post-ovulatory wound healing of hOSE cells are mediated by different signalling transduction pathways. The p38 MAPK signalling pathway may have possible therapeutic benefit in inflammation-associated disorders of the ovary, including cancer.

Original languageEnglish
Pages (from-to)273-283
Number of pages11
JournalJournal of Endocrinology
Issue number3
Publication statusPublished - Dec 2011


  • 3-Hydroxysteroid Dehydrogenases
  • Adult
  • Base Sequence
  • Cyclooxygenase 2
  • DNA Primers
  • Epithelial Cells
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-1alpha
  • Interleukin-4
  • MAP Kinase Signaling System
  • Middle Aged
  • NF-kappa B
  • Ovary
  • Protein-Lysine 6-Oxidase
  • RNA, Messenger
  • Receptors, Androgen
  • Signal Transduction
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases


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