Ghosh Debabrata, Najwa Abdul Rashid, Sengupta Jayasree
Department of Physiology, All India Institute of Medical Sciences, New Delhi.
Indian J Physiol Pharmacol. 2006 Oct-Dec;50(4):355-66.
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that is known to play an important role in blastocyst implantation. The putative action of LIF in the regulation of uterine function has been examined using mid-secretory stage monkey endometrial stromal cells cultured on rat-tail collagen type I and treated with recombinant human LIF (rhLIF) or immunoneutralized LIF (in LIF) under serum-free condition. Long-term ovariectomized rhesus monkeys (n=8) underwent simulation of their menstrual cycles with steroid hormones and endometrial tissue samples were collected on cycle day 18; stromal cells were isolated and grown in primary culture on three-dimensional collagen matrix. Significant decline in cellular protein synthesis (P < 0.01) and cell proliferation index (P < 0.05) was observed in cells with increasing doses (0-1000 ng/ml) of rhLIF under serum-free in vitro condition. JAK1 expression in cultured cells increased (P < 0.01) in response to rhLIF as revealed from Western blot and confocal laser scanning microscopic examination, STAT1 and STAT2 expressions were unchanged, while pSTAT3 expression increased (P < 0.01) with increased concentration of rhLIF in culture medium. Autophosphorylation of JAK1 in endometrial stromal cells showed no change with increasing concentration (0.01 to 100 ng/ml) of rhLIF in vitro, but significant (P < 0.05) increase was observed with the time of exposure to rhLIF. Immunoneutralization of LIF or no addition of rhLIF to cultured cells led to significant (P < 0.01) increase in stromal cell proliferation index and significant (P < 0.01) decrease in the level of JAK1 and its autophosphorylation as compared to cells exposed to rhLIF alone. From the present set of experiments we conclude that rhLIF affects the physiological behaviour of monkey mid secretory stage endometrial stromal cells in vitro via the JAK-STAT signaling pathway.
白血病抑制因子（LIF）是一种多效性细胞因子，已知其在胚泡着床中起重要作用。利用在I型大鼠尾胶原上培养的分泌中期猴子宫内膜基质细胞，在无血清条件下用重组人LIF（rhLIF）或免疫中和的LIF（in LIF）处理，研究了LIF在调节子宫功能中的假定作用。长期卵巢切除的恒河猴（n = 8）用类固醇激素模拟其月经周期，并在周期第18天收集子宫内膜组织样本；分离基质细胞并在三维胶原基质上进行原代培养。在无血清体外条件下，随着rhLIF剂量增加（0 - 1000 ng/ml），细胞蛋白合成（P < 0.01）和细胞增殖指数（P < 0.05）显著下降。蛋白质印迹和共聚焦激光扫描显微镜检查显示，rhLIF处理后培养细胞中JAK1表达增加（P < 0.01），STAT1和STAT2表达未改变，而随着培养基中rhLIF浓度增加，pSTAT3表达增加（P < 0.01）。体外随着rhLIF浓度增加（0.01至100 ng/ml），子宫内膜基质细胞中JAK1的自磷酸化无变化，但随着暴露于rhLIF的时间延长，观察到显著增加（P < 0.05）。与单独暴露于rhLIF的细胞相比，LIF免疫中和或不向培养细胞中添加rhLIF导致基质细胞增殖指数显著增加（P < 0.01），JAK1水平及其自磷酸化显著降低（P < 0.01）。从本实验中我们得出结论，rhLIF通过JAK - STAT信号通路影响体外猴分泌中期子宫内膜基质细胞的生理行为。
