Urokinase induces matrix metalloproteinase-9/gelatinase B expression in THP-1 monocytes via ERK1/2 and cytosolic phospholipase A2 activation and eicosanoid production.

Objective: Urokinase-type plasminogen activator (uPA) regulates cell migration and invasion by pericellular proteolysis and signal transduction events. We characterized the mechanisms by which uPA regulates matrix metalloproteinase-9 (MMP9) function in THP-1 monocytes.

Methods And Results: In THP-1 monocytes, MMP9 production induced by urokinase was completely inhibited by the ERK1/2 inhibitor, PD98059, but not by the p38 mitogen-activated protein kinase inhibitor, SB202190.

Urokinase upregulates matrix metalloproteinase-9 expression in THP-1 monocytes via gene transcription and protein synthesis.

Urokinase-type plasminogen activator (uPA) is suggested to exert its proliferatory, migratory and invasive action through binding with its membrane receptor, promoting pericellular proteolysis and mediating cell signal transduction. One of the possible actions of urokinase can be related to the regulation of activity and/or the expression of proteolytic enzymes participating in extracellular matrix degradation. In the present study, the role of uPA in regulating matrix metalloproteinase (MMP) expression and release by the monocyte cell line THP-1 was investigated.