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

Abstract

Constitutive tumor necrosis factor-α expression (TNF-α) has been detected in first trimester trophoblast cells and differentiated syncytiotrophoblasts. However, molecules which induce TNF-α 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-α expression in proliferating cytotrophoblastic cells and purified term trophoblasts. Both IL-1α and β stimulate TNF-α release from BeWo cells and TNF-α mRNA was transiently expressed. In growth-arrested/differentiated BeWo cells TNF-α mRNA was detectable without inducer, however, in the presence of IL-1β TNF-α secretion was weakly stimulated compared to proliferating cells. Cycloheximide strongly increased IL-1β-induced TNF-α mRNA concentration indicating that de novo protein synthesis is not required for TNF-α gene expression. However, treatment with cycloheximide did not prevent IL-1β-stimulated release of TNF-α, indicating that the cytokine can regulate TNF-α secretion at a posttranslational level, independently of TNF-α mRNA induction. Besides demonstration of this novel mechanism of IL-1-stimulated TNF-α expression, our data indicate an important role of IL-1 in TNF-α production of cytotrophoblastic cells.©1997 Federation of European Biochemical Societies.