Protein kinase C stimulates release of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by human decidual cells.
OBJECTIVE
Increased concentrations of amniotic fluid matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 have been observed in the context of premature rupture of membranes (PROM) and microbial invasion of the amniotic cavity. However, the source of the stimuli that contribute to the accumulation of these proteins in amniotic fluid remains to be identified. The present study was conducted to investigate MMP-2, MMP-9 and TIMP-1 secretion by decidual cells in response to activated protein kinase C (PKC).


METHODS
Decidual cells were isolated from term placentae, grown to confluence and incubated with control media or 10(-11) to 10(-8) mol/l concentrations of phorbol 12-myristate 13-acetate (PMA). Concentrations of MMP-2, MMP-9 and TIMP-1 in the culture supernatant were determined using sensitive and specific immunoassays. Substrate zymography was conducted to confirm MMP-9 assays.


RESULTS
PMA induced a concentration-dependent stimulation of release of MMP-9 (control vs. PMA l0(-9) and 10(-8) mol/l; p < 0.01) and TIMP-1 (control vs. PMA 10(-9) and 10(-8) mol/l; p < 0.001), but not MMP-2. A direct positive correlation was observed between MMP-9 and TIMP-1 release (r = 0.645; p < 0.001). Substrate zymography confirmed increased release of MMP-9 in response to PMA (control vs. PMA 10(-8) and PMA 10(-7) mol/l; p < 0.01).


CONCLUSIONS
Activation of PKC within the decidua will result in enhanced MMP-9 release, which upon activation could contribute to degradation of matrices within fetal membranes leading to PROM.
Edwin
S S
SS
Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Romero
R
R
Rathnasabapathy
C M
CM
Athaydel
N
N
Armant
D R
DR
Subramanian
M G
MG
D000653:Amniotic Fluid / Q000737:chemistry; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis / Q000378:metabolism*
D019714:Tissue Inhibitor of Metalloproteinases; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9