INDUCTION AND POSTTRANSLATIONAL EXPRESSION OF CYTOKINES IN A FIRST-TRIMESTER TROPHOBLAST CELL-LINE BY LIPOPOLYSACCHARIDE

OBJECTIVES: The response to injection by human first-trimester trophob lasts is a poorly understood event. This study was undertaken to deter mine 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 mu g/ml) or m edia alone for either 0, 2, 4, 6, 8, or 24 hours. Northern analysis wa s conducted by use of a panel of antisense cytokine probes. Enzyme-lin ked immunosorbent assays specific for either interleukin-1 alpha, inte rleukin-6, interleukin-8, or transforming growth factor-beta 1 were co nducted on corresponding cell culture supernatants, and the kinetics o f expression were determined. RESULTS: Interleukin-1 alpha, interleuki n-6, interleukin-8, and transforming growth factor-beta 1 transcriptio n occurred maximally between 2 and 8 hours of culture in media contain ing lipopolysaccharide, with a subsequent diminution of response. Enzy me-linked immunosorbent assay analysis corroborated lipopolysaccharide induction seen at the level of transcription, with significant posttr anslational expression of these cytokines being detected between 2 and 24 hours in culture (p < 0.01), CONCLUSIONS: Expression of the proinf lammatory cytokines interleukin-1 alpha, interleukin-6, interleukin-8 and transforming growth factor-beta 1 strongly support the contention that human first-trimester trophoblasts are capable of responding to a n infection stimulus and eliciting an immune response through cytokine -based immune signaling.