Tumor necrosis factor-alpha stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells.
To investigate the role of tumor necrosis factor-alpha (TNF alpha) in advanced collagenolysis and degradation of connective tissue components in preterm parturition, the effects of human recombinant TNF alpha (hrTNF alpha) on the production of matrix metalloproteinase 1 (MMP-1)/tissue collagenase, MMP-3/stromelysin, tissue inhibitor of metalloproteinases (TIMP), urokinase type-plasminogen activator (uPa) and prostaglandin (PG) E2 in human chorionic cells were examined in vitro. Human chorionic cells, but not amniotic cells, were found to respond to macrophage-conditioned medium (contains mainly interleukin 1) to produce MMP-1 and MMP-3. This indicated that the chorionic cell is one of the MMP-producing cells of fetal membranes. When confluent chorionic cells were treated with hrTNF alpha, the production of MMP-1 and MMP-3 as well as of uPa and PGE2 was greatly increased in a dose-dependent manner. In contrast, the production of TIMP was suppressed by hrTNF alpha. These results suggested that TNF alpha may participate in destruction of collagen and other connective tissue matrix components of fetal membranes and in promotion of uterine contractility in preterm parturition with intraamniotic infection.
So
T
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Department of Obstetrics and Gynecology, School of Medicine, Toho University, Tokyo, Japan.
Ito
A
A
Sato
T
T
Mori
Y
Y
Hirakawa
S
S
D000650:Amnion / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002823:Chorion / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D020781:Matrix Metalloproteinase 1; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010960:Plasminogen Activators / Q000096:biosynthesis*; D015849:Plasminogen Inactivators / Q000378:metabolism; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D003012:Microbial Collagenase; D020781:Matrix Metalloproteinase 1