Interleukin-1 stimulates tumor necrosis factor-alpha (TNF-alpha) release from cytotrophoblastic BeWo cells independently of induction of the TNF-alpha 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.
Knöfler
M
M
Department of Obstetrics and Gynecology, University of Vienna, Austria. Martin.Knoefler@akh-wien.ac.at
Kiss
H
H
Mösl
B
B
Egarter
C
C
Husslein
P
P
D002822:Choriocarcinoma / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha