Objective:To test the hypothesis that interleukin- 1β (IL-β) and tumor necrosis factor-α (TNF-α) regulate granulocyte colony-stimulating factor (G-CSF) production by by human placental villous core mesenchymal cells.
Methods:Villous core mesenchymal cells were isolated from placents at 14-20 weeks' gestation and cultured in vitro. Cells were treated with IL-1β or TNF-α in dose-response and time-course studies. We measured G-CSF mRNA expression by Northem blot analysis and G-CSF protein production by enzyme-linked immunosorbent assay of the conditioned media.
Results:Unstimulated mesenchmal cells expressed negligible G-CSF, Steady-state G-CSF mRNA expression was maximal 3-6 hours after IL-1β treatment and 6-18 hours after TNF-α treatment. Each cytokine induced G-CSF protein production in dose- and time-dependent manners, with IL-1β more potent than TNF-α. The G-CSF mRNA expression and G-CSf production induced by the combination of both cytokines exceeded that induced by either cytokine alone.
Conclusions:Interleukin-1β and TNF-α 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 response to these two cytokines.
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