Induction and posttranslational expression of cytokines in a first-trimester trophoblast cell line by lipopolysaccharide

Objectives: The response to infection by human first-trimester trophoblasts is a poorly understood event. This study was undertaken to determine whether first-trimester trophoblasts are capable of responding to an infection stimulus and mediating an immune response. Study Design: HTR-8/SVneo cells were exposed to lipopolysaccharide (1 μg/ml) or media alone for either 0, 2, 4, 6, 8, or 24 hours. Northern analysis was conducted by use of a panel of antisense cytokine probes. Enzyme-linked immunosorbent assays specific for either interleukin-1α, interleukin-6, interleukin-8, or transforming growth factor-β1 were conducted on corresponding cell culture supernatants, and the kinetics of expression were determined. Results: Interleukin-1α, interleukin-6, interleukin-8, and transforming growth factor-β1 transcription occurred maximally between 2 and 8 hours of culture in media containing lipopolysaccharide, with a subsequent diminution of response. Enzyme-linked immunosorbent assay analysis corroborated lipopolysaccharide induction seen at the level of transcription, with significant posttranslational expression of these cytokines being detected between 2 and 24 hours in culture (p<0.01). Conclusions: Expression of the proinflammatory cytokines interleukin-1α, interleukin-6, interleukin-8 and transforming growth factor-β1 strongly support the contention that human first-trimester trophoblasts are capable of responding to an infection stimulus and eliciting an immune response through cytokine-based immune signaling.