Down Modulation of TNF-α mRNA Placental Expression by AZT Used for the Prevention of HIV-1 Mother-to-Child Transmission

• Main Authors: Pornprasert S., Faye A., Mary J.Y., Dolcini G., Leechanachai P., Chaouat G., Ngo N., Barre-Sinoussi F., Menu E.
• Format: Article
• Language: English
• Published: 2014
• Online Access: http://www.scopus.com/inward/record.url?eid=2-s2.0-33747155554&partnerID=40&md5=9f241b894afea74f79a5eb96a85112c2; http://cmuir.cmu.ac.th/handle/6653943832/706
• Institution: Chiang Mai University

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 2000 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 (β-hCG) gene, lipopolysaccharide (LPS) activation, and microscopic examination. AZT at 2000 ng/ml significantly down-regulated TNF-α mRNA expression at day 1 and day 4, but had no effect on β-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-α mRNA expression. Down-regulation of TNF-α 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. © 2005 Elsevier Ltd. All rights reserved.