Poly(I:C) stimulates cytokine production, but not cell migration, in an extravillous trophoblast cell line

Abstract

Extravillous trophoblasts play an important role during pregnancy due to their involvement in spiral artery remodeling and immune privilege. Extravillous trophoblast dysfunction is thus implicated in a variety of pregnancy complications, such as those arising after maternal immune activation caused by infection. The aim of this study was to improve our understanding of how viral infection might affect extravillous trophoblast functioning. In a randomized, blinded set-up, cells of the extravillous trophoblast cell line HTR8/SVneo were exposed to polyinosinic polycytidylic acid (poly(I:C)), a viral mimetic that acts as a toll-like receptor (TLR)-3 agonist. After exposure of the cells to poly(I:C) in concentrations up to 200 µg/ml, analyses were performed for cytotoxicity, interleukin(IL)-1β, IL-6, IL-8, RANTES, interferon-γ, tumor necrosis factor-α, human chorionic gonadotropin, progesterone, estradiol and cell migration. Exposure to poly(I:C) led to a significant increase in IL-6, IL-8 and RANTES concentrations in HTR8/SVneo cell culture supernatant, but did not significant affect concentrations of other cytokines included for measurement. Similarly, exposure to poly(I:C) did not affect hormone secretion or cellular migration. While poly(I:C) is capable of triggering the release of cytokines in HTR8/SVneo cells, the absence of an effect on migration suggests that the core function of extravillous trophoblasts might not be affected by TLR-3 stimulation. These results indirectly suggest that IL-6, IL-8 and RANTES do not affect migration either. Future research is recommended to include a wide variety of immunological triggers to better map which ones may be relevant to extravillous trophoblast dysfunction.