Effect of Pro-inflammatory Cytokines on Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 2 in Cultured Human Term Placental Trophoblast and Human Choriocarcinoma JEG-3 Cells
Restricted accessResearch articleFirst published online July, 2005
Effect of Pro-inflammatory Cytokines on Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 2 in Cultured Human Term Placental Trophoblast and Human Choriocarcinoma JEG-3 Cells
Objective: 1 β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) is thought to act as a placental barrier protecting the fetus from high levels of maternal cortisol. On the other hand, intrauterine infection is one of the main causes of preterm birth and adverse fetal outcome, and pro-inflammatory cytokines may contribute to these adverse effects. However, the effect of pro-inflammatory cytokines on 11β-HSD2 is still not clear. Therefore, we have evaluated the effect of tumor necrosisfactor-α (TNF-α) and interleukin-1β (IL-1β) on 11β-HSD2 in cultured human placental trophoblast and in human choriocarcinoma JEG-3 cells.
Methods: Placental trophoblast cells were isolatedfrom human term placenta. Placental trophoblast cells and JEG-3 cells were treated with TNF-α (0.1-10 ng/mL) or IL-1β (0.1-10 ng/mL). Real-time reverse transcription polymerase chain reaction and Western blot were used to study the regulation of 1 11β-HSD2 expression. 11β-HSD2 activity was determined by measuring the rate of cortisol to cortisone conversion in the culture medium using thin-layer chromatography (TLC).
Results: In placental trophoblast, TNF-α and IL-1β down-regulated 11β-HSD2 mRNA expression and activity (both P <.05). The protein level was decreased only with IL-1β (P <.05). In JEG-3 cells, 11β-HSD2 mRNA was decreased by TNF-α but up-regulated by IL-1β, with no significant change in protein expression and activity.
Conclusion: Our results suggest caution in interpreting data using JEG-3 cells. However, our studies with primary trophoblast suggest that TNF-α and IL-1β may increase the amount of cortisol crossing to the placenta and fetal circulation by attenuating 11β-HSD2 activity, potentially contributing to preterm labor and altered fetal outcome in uterine infection.
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