Regulation of trophoblast invasion by IL-1β and TGF-β1

PROBLEM: To investigate the effect of IL-1beta and TGF-beta1 on trophoblast derived proteases and their inhibitors at the mRNA and protein level for elucidation of the mechanism of trophoblast invasion. METHOD OF STUDY: Trophoblast derived proteases and their inhibitors were localized in human placental villi by immunohistochemistry, their regulation at mRNA and protein levels were studied using RT-PCR and zymography, respectively, on trophoblast cells in culture. RESULTS: Trophoblast proteases, matrix metalloproteases (MMP-2, MMP-9), membrane type matrix metalloproteases (MT-MMP1&2) and urokinase type plasminogen activator (uPA) were found to be up regulated by IL-1beta while the protease inhibitors, tissue inhibitor of metalloproteases (TIMP-1 & 2) and plasminogen activator inhibitors (PAI-1 & 2) to be up regulated by TGF-beta1. CONCLUSION: Temporo-spatial regulation of trophoblast invasion is the outcome of a balanced interplay between the proteases and their cognate inhibitors. IL-1beta and TGF-beta1 seem to be critical for regulating the protease network thereby effectively controlling the extent to which the trophoblast may invade the maternal endometrium.