Department of Pediatrics-Neonatology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Am J Reprod Immunol. 2009 Dec;62(6):390-9. doi: 10.1111/j.1600-0897.2009.00756.x. Epub 2009 Oct 11.
Intra-uterine infections increase production of pro-inflammatory cytokines. It is unclear whether different infectious agents determine the relative expression of pro-and anti-inflammatory cytokines.
We compared the placental inflammatory response induced by bacterial lipopolysaccharide (LPS, endotoxin from Gram-negative bacteria) with those induced by lipoteichoic acid (LTA, a cell wall component of Gram-positive bacteria). Placental explants from term delivery were treated with either LPS or LTA, in the presence or absence of IL-10, for 24 hrs. Cytokines, prostaglandin E(2) (PGE(2)) production and cyclo-oxygenase-2 (COX-2) expression were quantified.
Both LTA and LPS significantly induced several cytokines with LPS eliciting more potent effects. IL-6 and IL-8 were induced to comparable levels in response to both LTA and LPS whereas monocyte chemotactic protein-1 (MCP-1) production was induced more by LTA, demonstrating a differential placental response to a specific toll-like receptor (TLR) ligand. IL-10 treatment significantly reduced most pro-inflammatory cytokines as well as PGE(2) induced by both LPS and LTA. Interestingly, IL-10 down-regulated LTA-mediated MCP1 induction, but not that mediated by LPS. Moreover, IL-10 was more effective in down-regulating PGE(2) after LPS- when compared with LTA stimulation.
Our results demonstrate that placental exposure to LTA and LPS appear to trigger distinct cytokine responses that can be modulated by IL-10.
宫内感染会增加促炎细胞因子的产生。目前尚不清楚不同的感染因子是否决定了促炎和抗炎细胞因子的相对表达。
我们比较了细菌脂多糖（LPS，革兰氏阴性菌的内毒素）和脂磷壁酸（LTA，革兰氏阳性菌细胞壁成分）引起的胎盘炎症反应。来自足月分娩的胎盘组织在存在或不存在白细胞介素 10（IL-10）的情况下，用 LPS 或 LTA 处理 24 小时。定量检测细胞因子、前列腺素 E2（PGE2）的产生和环氧化酶-2（COX-2）的表达。
LTA 和 LPS 均显著诱导了几种细胞因子，而 LPS 引起的作用更强。LTA 和 LPS 均可诱导产生相当水平的白细胞介素 6（IL-6）和白细胞介素 8（IL-8），而单核细胞趋化蛋白-1（MCP-1）的产生则更多地受到 LTA 的诱导，表明对特定 Toll 样受体（TLR）配体的胎盘反应存在差异。IL-10 处理显著降低了由 LPS 和 LTA 诱导的大多数促炎细胞因子和 PGE2。有趣的是，IL-10 下调了由 LTA 介导的 MCP1 诱导，但不影响由 LPS 介导的 MCP1 诱导。此外，与 LTA 刺激相比，IL-10 在 LPS 刺激后下调 PGE2 的效果更明显。
我们的研究结果表明，胎盘暴露于 LTA 和 LPS 似乎会引发不同的细胞因子反应，这些反应可被白细胞介素 10 调节。
