Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, and Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
Anesthesiology. 2012 Sep;117(3):568-79. doi: 10.1097/ALN.0b013e31826150a9.
We sought to elucidate the antiinflammation effect of human placental multipotent mesenchymal stromal cells (hPMSCs) and the possible molecular mechanisms.
Immortalized murine macrophages (RAW264.7 cells), with or without hPMSCs coincubation, were treated with endotoxin to induce expression of the relevant molecules.
The peak concentrations (means ± SD) of inflammatory molecules in endotoxin-activated macrophages with hPMSCs coincubation were significantly lower than those in endotoxin-activated macrophages without hPMSCs coincubation (tumor necrosis factor-α: 9.4±0.8 vs. 13.0±1.1 ng/ml; interleukin-6: 0.8±0.1 vs. 1.2±0.1 ng/ml; macrophage inflammatory protein-2: 345±30 vs. 666±51 ng/ml; intercellular adhesion molecule 1: 1.4±0.1 vs. 1.7±0.1 ng/ml; prostaglandin E2: 5.7±0.3 vs. 8.5±0.6 ng/ml; all P<0.008). Data of the activation of nuclear factor-κB and mitogen-activated protein kinases as well as the interaction between toll-like receptor 4 and myeloid differentiation primary response gene 88 paralleled those of the inflammatory molecules. In contrast, the endotoxin binding and toll-like receptor 4/myeloid differential-2 complex activation in endotoxin-activated macrophages with hPMSCs coincubation were comparable with those in endotoxin-activated macrophages without hPMSCs coincubation. As our data revealed that hPMSCs could induce low-grade prostaglandin E2 expression in macrophages, we also employed the selective cyclooxygenase-2 inhibitor NS-398 to further elucidate the possible role of prostaglandin E2. Our data revealed that the above-mentioned hPMSC-triggered inhibitory effects were significantly reversed by NS-398.
The antiinflammation effect of human placental multipotent mesenchymal stromal cells is mediated, at least in part, by prostaglandin E2 via a myeloid differentiation primary response gene 88-dependent pathway.
我们旨在阐明人胎盘间充质基质细胞（hPMSCs）的抗炎作用及其可能的分子机制。
用脂多糖（LPS）诱导永生化的鼠巨噬细胞（RAW264.7 细胞）及其与 hPMSCs 共培养物中相关分子的表达。
与 LPS 激活的无 hPMSCs 共培养物的巨噬细胞相比，LPS 激活的与 hPMSCs 共培养物的巨噬细胞中炎症分子的峰值浓度（均值±标准差）显著降低（肿瘤坏死因子-α：9.4±0.8 对 13.0±1.1ng/ml；白细胞介素-6：0.8±0.1 对 1.2±0.1ng/ml；巨噬细胞炎症蛋白-2：345±30 对 666±51ng/ml；细胞间黏附分子 1：1.4±0.1 对 1.7±0.1ng/ml；前列腺素 E2：5.7±0.3 对 8.5±0.6ng/ml；均 P<0.008）。核因子-κB 和丝裂原活化蛋白激酶的激活数据以及 Toll 样受体 4 和髓样分化初级反应基因 88 之间的相互作用与炎症分子相似。相反，LPS 激活的与 hPMSCs 共培养物的巨噬细胞中 LPS 结合和 Toll 样受体 4/髓样分化差异-2 复合物的激活与 LPS 激活的无 hPMSCs 共培养物的巨噬细胞中相似。由于我们的数据表明 hPMSCs 可诱导巨噬细胞产生低水平的前列腺素 E2，我们还采用选择性环氧化酶-2 抑制剂 NS-398 进一步阐明前列腺素 E2 可能的作用。我们的数据表明，上述 hPMSC 触发的抑制作用被 NS-398 显著逆转。
人胎盘多能间充质基质细胞的抗炎作用至少部分是通过前列腺素 E2 通过髓样分化初级反应基因 88 依赖途径介导的。
