title: IL1α and IL4 signalling in human ovarian surface epithelial cells.
abstract: 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.
authors: The Queen's Medical Research Institute, Centre for Reproductive Biology, Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors: Georgia
authors: G
authors: Papacleovoulou
authors: Hilary O D
authors: HO
authors: Critchley
authors: Stephen G
authors: SG
authors: Hillier
authors: J Ian
authors: JI
authors: Mason
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D051546:Cyclooxygenase 2 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053582:Interleukin-1alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; C508584:IL1A protein, human; C508598:IL4 protein, human; D053582:Interleukin-1alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D011944:Receptors, Androgen; D015847:Interleukin-4; D015096:3-Hydroxysteroid Dehydrogenases; D051546:Cyclooxygenase 2; D008249:Protein-Lysine 6-Oxidase; D048051:p38 Mitogen-Activated Protein Kinases