INTERLEUKIN-1 STIMULATES TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) RELEASE FROM CYTOTROPHOBLASTIC BEWO CELLS INDEPENDENTLY OF INDUCTION OF THE TNF-ALPHA MESSENGER-RNA

Constitutive tumor necrosis factor-alpha expression (TNF-alpha) has be en detected in first trimester trophoblast cells and differentiated sy ncytiotrophoblasts. However, molecules which induce TNP-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 t rophoblast development, induces TNF-alpha expression in proliferating cytotrophoblastic cells and purified term trophoblasts, Both IL-1 alph a and beta stimulate TNF-alpha release from BeWo cells and TNP-alpha m RNA was transiently expressed. In growth-arrested/differentiated BeWo cells TNF-alpha mRNA was detectable without inducer, however, in the p resence of IL-1 beta TNF-alpha secretion was weakly stimulated compare d to proliferating cells. Cycloheximide strongly increased IL-1 beta-i nduced TNF-alpha mRNA concentration indicating that de novo protein sy nthesis is not required for TNF-alpha gene expression. However, treatm ent with cycloheximide did not prevent IL-1 beta-stimulated release of TNF-alpha, indicating that the cytokine can regulate TNF-alpha secret ion at a posttranslational level, independently of TNF-alpha mRNA indu ction, Besides demonstration of this novel mechanism of IL-1-stimulate d TNF-alpha expression, our data indicate an important role of IL-1 in TNF-alpha production of cytotrophoblastic cells. (C) 1997 Federation of European Biochemical Societies.