Interleukin-1 beta and tumor necrosis factor-alpha stimulate granulocyte colony-stimulating factor production by placental villous core mesenchymal cells.
OBJECTIVE
To test the hypothesis that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) regulate granulocyte colony-stimulating factor (G-CSF) production by human placental villous core mesenchymal cells.


METHODS
Villous core mesenchymal cells were isolated from placentas at 14-20 weeks' gestation and cultured in vitro. Cells were treated with IL-1 beta or TNF-alpha in dose-response and time-course studies. We measured G-CSF mRNA expression by Northern blot analysis and G-CSF protein production by enzyme-linked immunosorbent assay of the conditioned media.


RESULTS
Unstimulated mesenchymal cells expressed negligible G-CSF. Steady-state G-CSF mRNA expression was maximal 3-6 hours after IL-1 beta treatment and 6-18 hours after TNF-alpha treatment. Each cytokine induced G-CSF protein production in dose-and time-dependent manners, with IL-1 beta more potent than TNF-alpha. The G-CSF mRNA expression and G-CSF protein production induced by the combination of both cytokines exceeded that induced by either cytokine alone.


CONCLUSIONS
Interleukin-1 beta and TNF-alpha stimulate G-CSF production by placental villous core mesenchymal cells in vitro. These results identify a potential mechanism by which villous core mesenchymal cells mediate, in part, the placental response to these two cytokines.
Vandermolen
D T
DT
Department of Obstetrics and Gynecology, Medical College of Virginia, Richmond, USA.
Kauma
S W
SW
Turner
T T
TT
D015152:Blotting, Northern; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor