Hoogen, C.M. van den
Hinsbergh, V.W.M. van
Gaubius Laboratory Dept. of Periodontology, Univ. of Helsinki, Helsinki, Finland TNO Preventie en Gezondheid
|Source:||Fibrinolysis, SUPPL. 2, 10, 109-111|
Biology · doxycycline · tissue plasminogen activator · urokinase · conference paper · fibrinolysis · human · plasminogen activation · priority journal
Degradation and remodelling of the extracellular matrix is an essential feature in many pathophysiological processes, especially in invasive and angiogenesis-related diseases. At least two families of proteolytic enzymes have been suggested to play a role in this process: matrix metalloproteinases (MMPs) and plasminogen activators, in particular urokinase-type plasminogen activator (u-PA). Doxycycline, a tetracycline derivative, has been shown to be able to inhibit MMP catalytic activities, a function independent of its antimicrobial properties. In this study we show that doxycycline also inhibits the activation of plasminogen by urokinase (u-PA) or tissue-type plasminogen activator (t-PA) at concentrations of 25-50 μM. It did not affect the activity of plasmin itself or the amidolytic activity of u-PA. This observation extends the insight in the inhibitory effect of doxycycline on cellular proteolysis and may support the rationale for the use of doxycycline in the treatment of destructive diseases like rheumatoid arthritis.