Blumenstein M, Keelan J A, Bowen-Shauver J M, Mitchell M D
School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
J Mol Endocrinol. 2005 Aug;35(1):165-75. doi: 10.1677/jme.1.01767.
Decreased suppressors of cytokine signaling (SOCS) activity in human gestational tissues may play a part in the onset/progression of term labor. Since SOCS proteins negatively regulate cytokine-mediated inflammatory processes, we hypothesized that SOCS proteins are elevated in gestational tissues from spontaneous preterm deliveries with intrauterine infection. SOCS1, -2 and -3 mRNAs and proteins were detectable by RT-PCR and immunoblotting respectively, in preterm amnion, choriodecidua and placenta, irrespective of infection status. Immunoperoxidase staining localized SOCS1, -2 and -3 to all cell types of the gestational membranes, with infiltrating leukocytes reacting strongly in infected tissues. In villous placenta, SOCS was immunolocalized to the syncytiotrophoblast with marked staining of round mesenchymal cells, possibly Hofbauer cells. Nuclear SOCS staining was seen in amnion, chorion and placental syncytiotrophoblasts. SOCS proteins were, in general, significantly more abundant in placenta compared with amnion or choriodecidua. Placental SOCS1 and interleukin-1beta concentrations were positively correlated (r(2)=0.47; P<0.05). However, no changes in SOCS levels in any tissues were observed with intrauterine infection. The relatively large amounts of SOCS proteins in the placenta may reflect a placenta-specific immunoprotective response to minimize the elaboration and effects of cytokines with potential to harm the placenta and fetus. Lack of labor-associated changes in SOCS levels suggests that the regulation of SOCS expression in preterm gestational tissues differs from those at term, perhaps reflecting roles in regulating placental somatotropic responses.
人妊娠组织中细胞因子信号转导抑制因子(SOCS)活性降低可能在足月分娩的发动/进展中起作用。由于SOCS蛋白对细胞因子介导的炎症过程起负调节作用,我们推测在伴有宫内感染的自发性早产妊娠组织中SOCS蛋白水平升高。分别通过RT-PCR和免疫印迹法在早产羊膜、绒毛膜蜕膜和胎盘中检测到SOCS1、-2和-3的mRNA和蛋白,与感染状态无关。免疫过氧化物酶染色显示SOCS1、-2和-3定位于胎膜的所有细胞类型,在感染组织中浸润的白细胞反应强烈。在绒毛胎盘,SOCS定位于合体滋养层,圆形间充质细胞(可能是霍夫鲍尔细胞)有明显染色。在羊膜、绒毛膜和胎盘合体滋养层细胞中可见SOCS的核染色。一般来说,与羊膜或绒毛膜蜕膜相比,胎盘中SOCS蛋白含量明显更高。胎盘SOCS1和白细胞介素-1β浓度呈正相关(r(2)=0.47;P<0.05)。然而,宫内感染时未观察到任何组织中SOCS水平的变化。胎盘中相对大量的SOCS蛋白可能反映了胎盘特异性免疫保护反应,以尽量减少可能损害胎盘和胎儿的细胞因子的产生及其影响。SOCS水平缺乏与分娩相关的变化表明,早产妊娠组织中SOCS表达的调节与足月时不同,这可能反映了其在调节胎盘生长激素反应中的作用。