Ying Wang1, Yuan Zhang1, Ming-Qing Li2, Deng-Xuan Fan2, Xiao-Hui Wang1, Da-Jin Li1, Li-Ping Jin3. 1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China. 2. 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. 3. 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.
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. 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.
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-humanIL-25 neutralizing antibody, recombinant humanIL-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.