Pornprasert S, Faye A, Mary J Y, Dolcini G, Leechanachai P, Chaouat G, Ngo N, Barré-Sinoussi F, Menu E
Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawarorost Road, Muang, Chiang Mai 50200, Thailand.
Placenta. 2006 Sep-Oct;27(9-10):989-95. doi: 10.1016/j.placenta.2005.10.010. Epub 2005 Dec 13.
Mechanisms of HIV-1 in utero mother-to-child transmission (MTCT) protection provided by AZT are not completely understood. The placental cytokine network is involved in the control of HIV-1 in utero transmission but the effect of AZT on this network is unknown. To evaluate the effects of AZT on placental cytokine expression, the chorionic villi from HIV-1 uninfected women term placentae were cultured with 0, 100, and 2,000 ng/ml AZT. Tissue fragments were harvested at days 1, 4, and 7 to determine the level of cytokine mRNA by real-time RT-PCR. The viability and morphology of the placental histocultures were monitored by the expression of beta-human chorionic gonadotropin (beta-hCG) gene, lipopolysaccharide (LPS) activation, and microscopic examination. AZT at 2,000 ng/ml significantly down-regulated TNF-alpha mRNA expression at day 1 and day 4, but had no effect on beta-hCG, stromal cell-derived factor 1 (SDF-1), and IL-10 gene expression. AZT did not induce any deleterious impact on placental tissue structure. Furthermore, activation of chorionic villi by LPS for 24 h up-regulated IL-10 and TNF-alpha mRNA expression. Down-regulation of TNF-alpha mRNA could represent a mechanism through which AZT can decrease the risk of HIV-1 MTCT, in addition to its direct effect on HIV-1 replication.
齐多夫定（AZT）对人类免疫缺陷病毒1型（HIV-1）宫内母婴传播（MTCT）的保护机制尚未完全明确。胎盘细胞因子网络参与了HIV-1宫内传播的控制，但AZT对该网络的影响尚不清楚。为了评估AZT对胎盘细胞因子表达的影响，将来自未感染HIV-1的足月孕妇胎盘的绒毛膜绒毛与0、100和2000 ng/ml的AZT一起培养。在第1、4和7天收集组织碎片，通过实时逆转录聚合酶链反应（RT-PCR）测定细胞因子mRNA水平。通过β-人绒毛膜促性腺激素（β-hCG）基因的表达、脂多糖（LPS）激活和显微镜检查来监测胎盘组织培养物的活力和形态。2000 ng/ml的AZT在第1天和第4天显著下调肿瘤坏死因子-α（TNF-α）mRNA的表达，但对β-hCG、基质细胞衍生因子1（SDF-1）和白细胞介素-10（IL-10）基因表达没有影响。AZT对胎盘组织结构没有产生任何有害影响。此外，LPS激活绒毛膜绒毛24小时可上调IL-10和TNF-α mRNA的表达。TNF-α mRNA的下调可能是AZT降低HIV-1 MTCT风险的一种机制，此外它还对HIV-1复制有直接作用。
