title: Estrogen promotes the growth of decidual stromal cells in human early pregnancy.
abstract: Interleukin-24 (IL-24) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells. The present study aimed to elucidate the biological function of IL-24 and its receptors (IL-20R1, IL-20R2 and IL-22R1) in decidual stromal cells (DSCs) at human maternal-fetal interface. The DSCs behaviors in vitro were verified by viability (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptosis assay, respectively. Additionally, the effects of pregnancy-associated hormones on IL-24 and the effect of IL-24 on the correspondent functional molecules were investigated by ELISA, in-cell western and flow cytometry, respectively. Here we found that DSCs expressed IL-24 and its receptors, and IL-24 obviously suppressed the viability and stimulated the apoptosis in DSCs. On the contrary, both anti-IL-24 and IL-22R1 neutralizing antibodies markedly promoted growth and reduced the apoptosis. Estrogen but not progesterone could significantly decrease IL-24 but not its receptors, and these effects could be abolished by the antagonist of estrogen receptor beta (ERβ). IL-24 significantly restricted the stimulatory effect of estrogen on the viability, anti-apoptosis, anti-apoptosis gene Bcl-2 and proliferation relative gene Ki-67 in DSCs. Our study has demonstrated that IL-24/IL-20R2/IL-22R1 axis is involved in the regulation of estrogen/ERβ signaling on the growth of DSCs through up-regulating the expression of Bcl-2 and Ki67, which suggests that estrogen plays an important role in DSC growth of the early pregnancy through down-regulating IL-24.
authors: Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, No. 413, Zhaozhou Road, Shanghai 200011, China.
authors: Jun
authors: J
authors: Shao
authors: Ming-Qing
authors: MQ
authors: Li
authors: Yu-Han
authors: YH
authors: Meng
authors: Kai-Kai
authors: KK
authors: Chang
authors: Ying
authors: Y
authors: Wang
authors: Li
authors: L
authors: Zhang
authors: Da-Jin
authors: DJ
authors: Li
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D011247:Pregnancy; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects*; D055815:Young Adult; D000099180:Interleukin-24
chemical_list: D004967:Estrogens; D007378:Interleukins; D000099180:Interleukin-24
keywords: DSCs; IL-24; apoptosis; early pregnancy; estrogen receptor beta; viability