Regulation of trophoblast invasion by IL-1beta and TGF-beta1

Am J Reprod Immunol. 2002 Oct;48(4):210-9. doi: 10.1034/j.1600-0897.2002.01151.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Culture Media, Conditioned / metabolism
  • Embryo Implantation / physiology*
  • Endopeptidases / metabolism*
  • Immunohistochemistry
  • Interleukin-1 / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1
  • Trophoblasts / metabolism*


  • Culture Media, Conditioned
  • Interleukin-1
  • TGFB1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tissue Inhibitor of Metalloproteinase-2
  • Endopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9