title: Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through ERK1/2 and PI3K signaling pathways in human early pregnancy.
abstract: Chemokine CCL24, acting through receptor CCR3, is a potent chemoattractant for eosinophil in allergic diseases and parasitic infections. We recently reported that CCL24 and CCR3 are co-expressed by trophoblasts in human early pregnant uterus. Here we prove with evidence that steroid hormones estradiol (E), progesterone (P), and human chorionic gonadotropin (hCG), as well as decidual stromal cells (DSCs) could regulate the expression of CCL24 and CCR3 of trophoblasts. We further investigate how trophoblast-derived CCL24 mediates the function of trophoblasts in vitro, and conclude that CCL24/CCR3 promotes the proliferation, viability and invasiveness of trophoblasts. In addition, analysis of the downstream signaling pathways of CCL24/CCR3 show that extracellular signal-regulated kinases (ERK1/2) and phosphoinositide 3-kinase (PI3K) pathways may contribute to the proliferation, viability and invasiveness of trophoblasts by activating intracellular molecules Ki67 and matrix metallopeptidase 9 (MMP9). However, we did not observe any inhibitory effect on trophoblasts when blocking c-Jun N-terminal kinase (JNK) or p38 pathways. In conclusion, our data suggests that trophoblast-derived CCL24 at the maternal-fetal interface promotes trophoblasts cell growth and invasiveness by ERK1/2 and PI3K pathways. Meanwhile, pregnancy-related hormones (P and hCG), as well as DSCs could up-regulate CCL24/CCR3 expression in trophoblasts, which may indirectly influence the biological functions of trophoblasts. Thus, our results provide a possible explanation for the growth and invasion of trophoblasts in human embryo implantation.
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Hui
authors: H
authors: Li
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Yu-Han
authors: YH
authors: Meng
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Wen-Qing
authors: WQ
authors: Shang
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Li-Bing
authors: LB
authors: Liu
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Xuan
authors: X
authors: Chen
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Min-Min
authors: MM
authors: Yuan
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China.
authors: Li-Ping
authors: LP
authors: Jin
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China mqli@fudan.edu.cn djli@shmu.edu.cn.
authors: Ming-Qing
authors: MQ
authors: Li
authors: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Zhao Zhou Road 413, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, ChinaNPFPC Key Laboratory of Contraceptive Drugs & DevicesShanghai Institute of Planned Parenthood Research, Shanghai, China mqli@fudan.edu.cn djli@shmu.edu.cn.
authors: Da-Jin
authors: DJ
authors: Li
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D054423:Chemokine CCL24 / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C515484:CCL24 protein, human; D054423:Chemokine CCL24; D019869:Phosphatidylinositol 3-Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3