General Abstractsстатья из журнала
Аннотация: Problem: There is growing interest in the role of viral infections and their association with adverse pregnancy outcomes.While the trophoblast is permissive to viruses, little is known about their impact on the placenta.We previously established that the Toll-like receptor 8 (TLR8) agonist, viral ssRNA, induces a pro-inflammatory cytokine response in first trimester trophoblast.Thus, we sought to determine the mechanisms involved, and whether viral ssRNA could induce an antiviral response.Methods of study: The human first trimester trophoblast cell line, HTR8, was stably transfected to express either a TLR8 dominant negative (DN) or MyD88-DN.The wildtype, TLR8-DN or MyD88-DN cells were treated with or without viral ssRNA (5 µg/mL).After 12 hr, RNA was extracted and qRT-PCR performed for pro-inflammatory cytokines [IL-8, IL-6]; type I interferons [IFNa, IFNb], antiviral factors [2 0 ,5 0 -oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G)]; and antimicrobial peptides [secretory leukocyte protease inhibitor (SLPI), human beta defensin-1 (HBD1) and HBD2].Results: Treatment of wildtype trophoblast with ssRNA significantly increased mRNA for IL-6 by 8.3fold; IL-8 by 1.3-fold; IFNa by 2.6-fold; IFNb by 3.6fold; OAS by 1.4-fold; MxA by 2.5-fold; APOBEC3G by 2.2-fold; and SLPI by 2.3-fold, compared to untreated controls (P < 0.05).ssRNA had no effect on HBD1/2 expression.The TLR8-DN significantly inhibited ssRNA-induced IL-6 by 70.1%; IL-8 by 61.7%; IFNa by 48.1%; and SLPI by 58.6%, compared to wildtype cells (P < 0.05).Similarly, the MyD88-DN significantly inhibited ssRNA-induced IL-6 by 69.4%; IL-8 by 70%; IFNa by 64.6%; and SLPI by 55.4%.Viral ssRNA-induced upregulation of IFNb, OAS, MxA and APOBEC3G was unaffected by either the TLR8-DN or MyD88-DN.Conclusions: These findings demonstrate that viral ssRNA induces a trophoblast inflammatory cytokine, IFNa, and SLPI response through TLR8 and MyD88.In contrast, the ssRNA-induced IFNb and subsequent antiviral response occurs independently of the TLR8/ MyD88 pathway.
Год издания: 2014
Издательство: Wiley
Источник: American Journal of Reproductive Immunology
Ключевые слова: Reproductive System and Pregnancy
Открытый доступ: bronze
Том: 71
Страницы: 29–89