Effect of interferon gamma (IFN-ƒ×) on metalloproteinases (MMPs) in a model of embryo invasion

FONTANA, V.; BELLUSCIO, L.; CEBRAL, E.; CAMEO, M.; CALVO, JC.

Los Cocos, Córdoba, Argentina

Congreso; III Latin American Symposium on Maternal-Fetal Interaction and Placenta: Basic and Clinic Research (SLIMP); 2007

Asociación SLIMP

Trophoblastic cells express MMP-2 and -9, which digest the endometrial ECM during embryo invasion. MMPs could be spatial-temporally regulated by Th-1 or Th-2 type cytokines. We reported the effect of IFN-g (Th1), on murine embryo development in vitro and confirmed that JEG-3 cells (model for embryo invasion) express leptin and MMPs. Objective: to study the effect of IFN-g in trophoblastic invasion using MMPs expression and activity as indicators. JEG-3 cells were cultured for 3 days in the presence of IFN-g [0-160000 UI/ml]. We evaluated MMP-9 and 2 activities (zymograms) and MMP-9 and Leptin expression (Western blot). Activity of MMP-9 on cells cultured in the presence of IFN-g showed a significant decrease (p<0.0001 vs. Control, n=3, R=0.82), this was more evident at a concentration of 160000 U/ml. We observed a more marked decrease in MMP-2 activity compared to MMP-9 (vs. Control p< 0.0001). The maximum diminution on MMP-2 activity was observed at 160000 U/ml (p< 0.0001 vs. Control, n=3, R=0.97, Spearman Analysis two tails). The culture of cells in the presence of different concentration of IFN-g did not modify its effect on the expression of MMP-9. We also tested the expression of leptin in presence of IFN-g and observed that the amount of protein secreted to the culture medium was lower at 160000 UI/ml compared to the control. This effect correlates with the reduction on MMPs activity described before. Taking IFN-g as a TH1 cytokine related to the implantatory process, we demonstrated that IFN-g possible deleterious effects on the mother-embryo interaction could be related to an altered cell invasion by modifying the activity of MMP-2 and -9, without affecting the expression of MMP-9.