Interleukin‐1 stimulates tumor necrosis factor‐α (TNF‐α) release from cytotrophoblastic BeWo cells independently of induction of the TNF‐α mRNA

Constitutive tumor necrosis factor-alpha expression (TNF-alpha) has been detected in first trimester trophoblast cells and differentiated syncytiotrophoblasts. However, molecules which induce TNF-alpha release from these cells and their mechanism of action have not been defined. We show for the first time that interleukin-1 (IL-1), a regulator of trophoblast development, induces TNF-alpha expression in proliferating cytotrophoblastic cells and purified term trophoblasts. Both IL-1alpha and beta stimulate TNF-alpha release from BeWo cells and TNF-alpha mRNA was transiently expressed. In growth-arrested/differentiated BeWo cells TNF-alpha mRNA was detectable without inducer, however, in the presence of IL-1beta TNF-alpha secretion was weakly stimulated compared to proliferating cells. Cycloheximide strongly increased IL-1beta-induced TNF-alpha mRNA concentration indicating that de novo protein synthesis is not required for TNF-alpha gene expression. However, treatment with cycloheximide did not prevent IL-1beta-stimulated release of TNF-alpha, indicating that the cytokine can regulate TNF-alpha secretion at a posttranslational level, independently of TNF-alpha mRNA induction. Besides demonstration of this novel mechanism of IL-1-stimulated TNF-alpha expression, our data indicate an important role of IL-1 in TNF-alpha production of cytotrophoblastic cells.