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


METHODS
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.


CONCLUSIONS
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.
Karmakar
Subhradip
S
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Das
Chandana
C
D017077:Culture Media, Conditioned / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014327:Trophoblasts / Q000378:metabolism*
D017077:Culture Media, Conditioned; D007375:Interleukin-1; C508960:TGFB1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019716:Tissue Inhibitor of Metalloproteinase-2; D010450:Endopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9