Induction of the urokinase plasminogen activator system by oncostatin M promotes endothelial migration

Oncostatin M (OSM) is an inflammatory cytokine produced by activated macrop hages and T-lymphocytes. We have previously demonstrated that OSM-induced e ndothelial cell migration, unlike endothelial cell proliferation and spindl e formation, is independent of basic fibroblast growth factor expression (W ijelath et at. [1997] J. Cell. Sci. 110:871-879). To better understand the mechanism of OSM-induced endothelial cell migration, this study examined th e potential role of the plasminogen activator system in promoting OSM media ted endothelial cell migration. OSM stimulated increased mRNA levels of uro kinase-plasminogen activator (uPA) and urokinase-plasminogen activator rece ptor (uPAR) in a time and dose-dependent manner. Transcriptional run-off an d mRNA stability analysis demonstrated that the increase in uPA and uPAR mR NA levels was due to both increased gene transcription and mRNA stability. The increase in mRNA correlated with increased protein levels of both uPA a nd uPAR. This increase was reflected in elevated levels of membrane-bound p lasmin activity. OSM-induced endothelial cell migration was only partially dependent on plasmin activity since incubating endothelial cells without pl asminogen or, in the presence of aprotinin, resulted in suppression of endo thelial cell migration, indicating that OSM promoted endothelial cell migra tion through both a plasmin-dependent and independent mechanism. Our result s imply a role for OSM in promoting endothelial cell migration via a plasmi n-dependent pathway and a uPAR-mediated pathway. Together, these and other recent studies support a role for OSM in modulating the different phases of angiogenesis. (C) 2000 Wiley-Liss, Inc.