Down‐Regulation of TIMP 3 Leads to Increase in TACE Expression and TNF α Production by Placental Trophoblast Cells

Problem To determine whether down‐regulation of TIMP 3 expression promotes TACE expression and increases in TNF α production by placental trophoblast cells. Method of study Placental expression of TIMP 3 and TACE was examined by immunostaining and Western blot. Effects of TIMP 3 on TACE expression and TNF α production were assessed by transfection of TIMP 3 si RNA into trophoblasts isolated from normal placentas. Effects of oxidative stress on trophoblast TIMP 3 expression and TNF α production were also determined. Trophoblast production of TIMP 3, TACE and TNF α were measured by ELISA . Results TIMP 3 expression was markedly reduced in preeclamptic placentas compared with normal placentas; oxidative stress down‐regulated trophoblast TIMP 3 expression and production, P  < 0.01. Down‐regulation of TIMP 3 expression by TIMP 3 si RNA resulted in significant increases in TACE expression and TNF α production, P  < 0.01. Conclusion As TIMP 3 is an endogenous TACE inhibitor, down‐regulation of trophoblast TIMP 3 expression/activity could result in increased TACE expression and subsequently lead to increased TNF α production in preeclamptic placentas.