title: Interleukin-25 induced by human chorionic gonadotropin promotes the proliferation of decidual stromal cells by activation of JNK and AKT signal pathways.
abstract: OBJECTIVE
  To clarify the role and mechanism of interleukin (IL)-25 in regulating the biological functions of decidual stromal cells (DSCs) in human early pregnancy.
  
  
  METHODS
  Laboratory study of the effect of IL-25 induced by hCG on the proliferation of DSCs.
  
  
  METHODS
  Research laboratories.
  
  
  METHODS
  Women aged 23-47 years with normal pregnancy and abortion.
  
  
  METHODS
  None.
  
  
  METHODS
  Signal transduction from IL-25.
  
  
  RESULTS
  Here we show that DSCs coexpress IL-25/IL-17RB. Human chorionic gonadotropin promotes the expression of IL-25/IL-17RB. In contrast to anti-human IL-25 neutralizing antibody, recombinant human IL-25 (rhIL-25) significantly stimulates the proliferation of DSCs in dosage- and time-dependent manners. RhIL-25 promotes the phosphorylation of AKT, extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), and nuclear factor κB in DSCs. Interestingly, blocking JNK or AKT signal with inhibitors down-regulates the stimulatory effect on DSC proliferation induced by rhIL-25. In addition, the results of Western blot show that the expression of IL-25/IL-17RB in DSCs from normal pregnancy was higher than that from abortion.
  
  
  CONCLUSIONS
  Our results have revealed that hCG derived of trophoblasts up-regulates the expression of IL-25/IL-17RB in DSCs and that IL-25 further stimulates the proliferation of DSCs through activating JNK and AKT signals, which finally contributes to the establishment and maintenance of physiological pregnancy.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China.
authors.forename: Deng-Xuan
authors.initials: DX
authors.lastname: Fan
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China. Electronic address: jinliping2012@gmail.com.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jin
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D003656:Decidua / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D010766:Phosphorylation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; C408922:IL17RB protein, human; C486701:IL25 protein, human; D020381:Interleukin-17; D047428:Protein Kinase Inhibitors; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases
keywords: DSCs; IL-17RB; IL-25; early pregnancy; hCG; proliferation