Pentoxifylline attenuates HPV-16 associated necrosis in placental trophoblasts.
Arch Gynecol Obstet
; 291(3): 647-52, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25227658
ABSTRACT
PURPOSE:
Human papillomaviruses (HPV) have been associated with placental inflammation resulting in high-risk preterm birth. The premise for this study was that treatment with anti-inflammatory pentoxifylline would inhibit HPV-mediated placental cell death. The objectives were (1) to study the effects of HPV-16 exposure on trophoblast cells and (2) to evaluate pentoxifylline in preventing the damaging effects of HPV-16.METHODS:
Mouse embryos (1-cell) were cultured (G1plus medium, 72 h, 37 °C, 5 % CO2 in air), divided into four groups at blastocyst-stage and incubated to implantation stage. Implanted trophoblasts were exposed to either HPV-16 (group 1), concomitant HPV-16 and 3 mM pentoxifylline (group 2), 3 mM pentoxifylline only (group 3) or control medium (group 4) and further incubated for 24 h. HPV-16 were from SiHa cell lysates. Trophoblast structural integrity was assessed by morphometric analysis while apoptosis and necrosis were detected using dual-stain fluorescence assay.RESULTS:
Trophoblast outgrowth was reduced by 90% (P < 0.05) in HPV-16 presence (629 ± 265 µ(2), mean + SEM) when compared with controls (6,456 ± 795 µ(2)). Pentoxifylline attenuated the effects of HPV-16 (4,308 ± 362 µ(2)). Nuclear size of HPV-16 infected trophoblasts was smallest among the groups (P < 0.005). HPV-16 decreased cell viability and increased necrosis but not apoptosis. Pentoxifylline prevented HPV-16 associated necrosis in trophoblasts.CONCLUSIONS:
HPV-16 decreased nuclear size and trophoblast outgrowth but these effects were attenuated by the phosphodiesterase inhibitor, pentoxifylline. The action of HPV-16 on trophoblasts was increased cell necrosis suggesting that HPV-16 pathogenesis involved either cAMP inhibition and/or activated TNF pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Implantação do Embrião
/
Pentoxifilina
/
Placenta
/
Trofoblastos
/
Sobrevivência Celular
/
Papillomavirus Humano 16
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Arch Gynecol Obstet
Assunto da revista:
GINECOLOGIA
/
OBSTETRICIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos