Activation of human progelatinase A/promatrix metalloproteinase 2 by Escherichia coli-derived serine proteinase.
Treatment of human uterine cervical fibroblasts with commercial lipopolysaccharide (LPS) preparations from different serotypes of Escherichia coli effectively augmented the processing of mammalian progelatinase A/promatrix metalloproteinase (proMMP)-2 to a 62-kDa form of MMP-2. When purified proMMP-2 was incubated with LPS preparations, the proenzyme was similarly processed into the 62-kDa active MMP-2 in a time- and dose-dependent manner. By contrast, progelatinase B/proMMP-9 and prostromelysin 1/proMMP-3 were not activated. A serine proteinase inhibitor, phenylmethylsulfonyl fluoride, completely interfered with this LPS-mediated activation of proMMP-2. This is novel evidence that E. coli serine proteinase is a specific activator of proMMP-2. Thus, it is very likely that E. coli infection plays a crucial role in the degradation of connective tissues via the activation of proMMP-2, and the resultant active MMP-2 participates in the dysfunction of connective tissues such as in the preterm rupture of fetal membranes.
Takeda
M
M
Department of Pharmacy, Tsukuba University Hospital, Amakubo, Tsukuba, Ibaraki, 305-8756, Japan.
Imada
K
K
Sato
T
T
Ito
A
A
D000818:Animals; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism*; D011817:Rabbits; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000494:pharmacology*
D004792:Enzyme Precursors; D008070:Lipopolysaccharides; D012697:Serine Endopeptidases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase