Yeganegi Maryam, Watson Carole S, Martins Andrew, Kim Sung O, Reid Gregor, Challis John R G, Bocking Alan D
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Am J Obstet Gynecol. 2009 May;200(5):532.e1-8. doi: 10.1016/j.ajog.2008.12.032. Epub 2009 Mar 14.
The objective of the study was to determine the effect of fetal sex on the output of cytokines and prostaglandin-regulating enzymes in lipopolysaccharide (LPS) and probiotic lactobacilli-treated placental trophoblast cells.
We examined the effect of LPS and Lactobacillus rhamnosus GR-1 supernatant in placental trophoblast cells on tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-10 using enzyme-linked immunosorbent assay and on prostaglandin-endoperoxide synthase 2 (PTGS2), 15-hydroxy prostaglandin dehydrogenase (PGDH), and toll-like receptor-4 (TLR-4) using Western blotting. Comparisons were performed using one-way analysis of variance and Student t test.
LPS increased the output of TNF-alpha, IL-10, and PTGS2 with a greater response in male placentae. L rhamnosus GR-1 supernatant inhibited the LPS-stimulated TNF-alpha and increased IL-10. It also up-regulated expression of PGDH in female placentae and partially reduced the LPS-stimulated PTGS2 in male placentae. There was no change in IL-1beta. Expression of TLR-4 was greater in placentae of male fetuses.
These findings suggest an underlying mechanism for the sex difference in the incidence of preterm birth and provide potential evidence for a therapeutic benefit of lactobacilli in reducing preterm labor.
本研究的目的是确定胎儿性别对脂多糖(LPS)和益生菌乳酸杆菌处理的胎盘滋养层细胞中细胞因子和前列腺素调节酶输出的影响。
我们使用酶联免疫吸附测定法检测了LPS和鼠李糖乳杆菌GR-1上清液对胎盘滋养层细胞中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10的影响,并使用蛋白质印迹法检测了对前列腺素内过氧化物合酶2(PTGS2)、15-羟基前列腺素脱氢酶(PGDH)和Toll样受体4(TLR-4)的影响。使用单因素方差分析和学生t检验进行比较。
LPS增加了TNF-α、IL-10和PTGS2的输出,雄性胎盘的反应更大。鼠李糖乳杆菌GR-1上清液抑制LPS刺激的TNF-α并增加IL-10。它还上调了雌性胎盘中PGDH的表达,并部分降低了雄性胎盘中LPS刺激的PTGS2。IL-1β没有变化。TLR-4在雄性胎儿的胎盘中表达更高。
这些发现提示了早产发生率性别差异的潜在机制,并为乳酸杆菌在减少早产方面的治疗益处提供了潜在证据。