Mita Shizuka, Nakakuki Masanori, Ichioka Masayuki, Shimizu Yutaka, Hashiba Masamichi, Miyazaki Hiroyasu, Kyo Satoru
Development Research, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan.
Development Research, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan.
Eur J Obstet Gynecol Reprod Biol. 2017 Jul;214:65-70. doi: 10.1016/j.ejogrb.2017.04.048. Epub 2017 Apr 29.
C-C motif chemokine ligand 20 is thought to contribute to the development of endometriosis by recruiting Th17 lymphocytes into endometriotic foci. The present study investigated the effects of dienogest, a progesterone receptor agonist used to treat endometriosis, on C-C motif chemokine ligand 20 expression by endometriotic cells.
Effects of dienogest on mRNA expression and protein secretion of C-C motif chemokine ligand 20 induced by interleukin 1β were assessed in three immortalized endometriotic epithelial cell lines, parental cells (EMosis-CC/TERT1), and stably expressing human progesterone receptor isoform A (EMosis-CC/TERT1/PRA+) or isoform B (EMosis-CC/TERT1/PRA-/PRB+).
Dienogest markedly inhibited interleukin 1β-stimulated C-C motif chemokine ligand 20 mRNA expression and protein secretion in EMosis-CC/TERT1/PRA-/PRB+, which was abrogated by the progesterone receptor antagonist RU486. In EMosis-CC/TERT1/PRA+, dienogest slightly inhibited C-C motif chemokine ligand 20 mRNA and protein. In EMosis-CC/TERT1, dienogest slightly inhibited C-C motif chemokine ligand 20 mRNA, but had no effect on C-C motif chemokine ligand 20 protein.
Dienogest inhibited interleukin 1β-induced up-regulation of C-C motif chemokine ligand 20 in endometriotic epithelial cells, mainly mediated by progesterone receptor B.
C-C基序趋化因子配体20被认为通过将Th17淋巴细胞募集到子宫内膜异位病灶中,促进子宫内膜异位症的发展。本研究调查了用于治疗子宫内膜异位症的孕激素受体激动剂地诺孕素对子宫内膜异位细胞C-C基序趋化因子配体20表达的影响。
在三种永生化子宫内膜异位上皮细胞系、亲代细胞(EMosis-CC/TERT1)以及稳定表达人孕激素受体亚型A(EMosis-CC/TERT1/PRA+)或亚型B(EMosis-CC/TERT1/PRA-/PRB+)中,评估地诺孕素对白细胞介素1β诱导的C-C基序趋化因子配体20 mRNA表达和蛋白分泌的影响。
地诺孕素显著抑制白细胞介素1β刺激的EMosis-CC/TERT1/PRA-/PRB+中C-C基序趋化因子配体20 mRNA表达和蛋白分泌,孕激素受体拮抗剂RU486可消除这种抑制作用。在EMosis-CC/TERT1/PRA+中,地诺孕素轻微抑制C-C基序趋化因子配体20 mRNA和蛋白。在EMosis-CC/TERT1中,地诺孕素轻微抑制C-C基序趋化因子配体20 mRNA,但对C-C基序趋化因子配体20蛋白无影响。
地诺孕素抑制白细胞介素1β诱导的子宫内膜异位上皮细胞中C-C基序趋化因子配体20的上调,主要由孕激素受体B介导。