Interleukin-25 induced by human chorionic gonadotropin promotes the proliferation of decidual stromal cells by activation of JNK and AKT signal pathways

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. Design Laboratory study of the effect of IL-25 induced by hCG on the proliferation of DSCs. Setting Research laboratories. Patient(s) Women aged 23–47 years with normal pregnancy and abortion. Intervention(s) None. Main Outcome Measure(s) Signal transduction from IL-25. Result(s) 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. Conclusion(s) 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.