Ontogeny of the expression and regulation of interleukin-6 (IL-6) and IL-1 mRNAs by human trophoblast cells during differentiation in vitro

During human placental differentiation, mononuclear cytotrophoblast cells fuse and differentiate into syncytiotrophoblast cells. Although syncytiotrophoblast cells have been shown to express interleukin-1α (IL-1α), IL-1β and IL-6, the pattern of expression of these cytokines during placental differentiation is unknown. We have examined the expression of IL-1α IL-1β and IL-6 mRNA during differentiation of cytotrophoblast cells in culture. IL-1α, IL-1β and IL-6 mRNA levels were determined by semiquantitative reverse transcription-PCR analysis using glyceraldehyde phosphate dehydrogenase as an internal control. All three cytokine mRNA levels decreased markedly during trophoblast differentiation. After 6 days in culture, when almost all the cytotrophoblast cells had fused and differentiated into syncytiotrophoblast cells, the amounts of IL-1α, IL-1β and IL-6 mRNA were decreased by 87.1, 72.1 and 60.9% respectively. Exogenous IL-6 had differential effects on cytokine mRNA expression. When added to placental cultures during the first 6 days of culture, IL-6 markedly inhibited IL-6, IL-1α and IL-1β mRNA expression. However, when added to the cells during days 6-9 of culture, when most of the cells were syncytiotrophoblast cells, IL-6 stimulated IL-1α and IL-1β mRNA expression. The results of these studies indicate that IL-1α, IL-1β and IL-6 mRNA expression decreases markedly during cytotrophoblast differentiation in vitro and that the regulation of trophoblast cytokine mRNA levels changes during differentiation.