Holmlund Ulrika, Wähämaa Heidi, Bachmayer Nora, Bremme Katarina, Sverremark-Ekström Eva, Palmblad Karin
Department of Immunology, The Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden.
Immunology. 2007 Nov;122(3):430-7. doi: 10.1111/j.1365-2567.2007.02662.x. Epub 2007 Jul 6.
High mobility group box protein 1 (HMGB1) was previously considered a strict nuclear protein, but lately data are accumulating on its extranuclear functions. In addition to its potent proinflammatory capacities, HMGB1 has a prominent role in a number of processes of specific interest for the placenta. Our overall aim was to investigate the expression of HMGB1 in human term placenta and elucidate a potential difference in HMGB1 expression comparing vaginal deliveries with elective Caesarean sections. In addition, placentas from normal pregnancies were compared with placentas from pregnancies complicated by pre-eclampsia. Twenty-five placentas, 12 from normal term pregnancies and 13 from pregnancies complicated by pre-eclampsia were analysed with immunohistochemistry for HMGB1 and its putative receptors; receptor for advanced glycation end-products (RAGE), Toll-like receptor 2 (TLR2) and TLR4. We present the novel finding that in addition to a strong nuclear HMGB1 expression in almost all cells in investigated placentas, an individual variation of cytoplasmic HMGB1 expression was detected in the syncytiotrophoblast covering the peripheral chorionic villi, by cells in the decidua and in amnion. Production of HMGB1 was confirmed by in situ hybridization. Although labour can be described as a controlled inflammatory-like process no differences in HMGB1 expression could be observed comparing active labour and elective Caesarean sections. However, a tendency towards a higher expression of cytoplasmic HMGB1 in the decidua from women with pre-eclampsia was demonstrated. The abundant expression of the receptors RAGE, TLR2 and TLR4 implicates a local capability to respond to HMGB1, although the precise role in the placenta remains to be elucidated.
高迁移率族蛋白B1（HMGB1）以前被认为是一种严格的核蛋白，但最近有关其核外功能的数据不断积累。除了其强大的促炎能力外，HMGB1在胎盘特别感兴趣的一些过程中也发挥着重要作用。我们的总体目标是研究HMGB1在足月人胎盘中的表达，并阐明经阴道分娩与择期剖宫产相比HMGB1表达的潜在差异。此外，还将正常妊娠胎盘与子痫前期妊娠胎盘进行了比较。采用免疫组织化学方法分析了25个胎盘，其中12个来自足月正常妊娠，13个来自子痫前期妊娠，检测HMGB1及其假定受体；晚期糖基化终产物受体（RAGE）、Toll样受体2（TLR2）和TLR4。我们有了一个新发现，除了在所研究的胎盘中几乎所有细胞中都有强烈的核HMGB1表达外，在覆盖外周绒毛膜绒毛的合体滋养层、蜕膜和羊膜细胞中检测到了细胞质HMGB1表达的个体差异。原位杂交证实了HMGB1的产生。尽管分娩可被描述为一个可控的炎症样过程，但比较活跃分娩和择期剖宫产时，未观察到HMGB1表达的差异。然而，子痫前期女性蜕膜中细胞质HMGB1表达有升高的趋势。受体RAGE、TLR2和TLR4的丰富表达表明局部有对HMGB1作出反应 的能力，尽管其在胎盘中的确切作用仍有待阐明。
