Plasmin-independent gelatinase B (matrix metalloproteinase-9) release by monocytes under the influence of urokinase.
It is shown that the release of matrix metalloproteinase-9 (gelatinase B) by THP-1 and U937 cells into conditioned media is increased under the action of recombinant single-chain urokinase. This effect is not accompanied by proteolytic activation of gelatinase B and is related to release of a pro-form of the enzyme. The action of urokinase on monocytes is time-dependent and becomes significant 12-24 h after the beginning of cell incubation. The dependence of the effect on the concentration of urokinase is characterized by half-maximum at about 20 nM and saturation at about 200 nM. The urokinase-induced gelatinase B release is not dependent on the action of plasmin because plasmin inhibitors aprotinin and alpha2-antiplasmin do not abolish this action. Additionally, tissue type plasminogen activator does not induce gelatinase B release by monocytes as observed under the action of urokinase. Nevertheless, the catalytic activity of urokinase participates in the development of the observed effect because it is significantly depressed by the natural urokinase inhibitor PAI-1. The effect of urokinase is completely abolished by actinomycin D and cycloheximide, indicating the participation of transcription and translation processes in its development.
Menshikov
M Y
MY
Institute of Experimental Cardiology, Cardiology Research Center, 3-ya Cherepkovskaya ul. 15a, Moscow, 121552 Russia. myumensh@cardio.ru
Elizarova
E P
EP
Kudryashova
E
E
Timofeyeva
A V
AV
Khaspekov
Y
Y
Beabealashvilly
R S
RS
Bobik
A
A
D007611:Aprotinin / Q000494:pharmacology; D002478:Cells, Cultured; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism* / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
D061965:Matrix Metalloproteinase Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D000979:alpha-2-Antiplasmin; D007611:Aprotinin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9