Down modulation of TNF-alpha mRNA placental expression by AZT used for the prevention of HIV-1 mother-to-child transmission.
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.
Pornprasert
S
S
Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawarorost Road, Muang, Chiang Mai 50200, Thailand.
Faye
A
A
Mary
J Y
JY
Dolcini
G
G
Leechanachai
P
P
Chaouat
G
G
Ngo
N
N
Barré-Sinoussi
F
F
Menu
E
E
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002824:Chorionic Villi / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008070:Lipopolysaccharides; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine