Cyclooxygenase-2 activity is necessary for the angiogenic properties of oncostatin M

Macrophages play a major role in angiogenesis, We recently reported that on costatin M (OSM), a cytokine of the interleukin (IL)-6 family secreted by m acrophages, has a potent angiogenic activity on human microvascular endothe lial cells (HMEC-1), but has no effect on macrovascular cells (human umbili cal vein endothelial cells (HUVECs)), In this work, we show that in HMEC-1, OSM (0.5-2.5 ng/ml), leukemia inhibitory factor (LIF) (25 ng/ml), bFGF (25 ng/ml) and IL-1 beta (5 ng/ml) induced production of cyclooxygenase (COX)- 2, In contrast, in HUVECs, neither OSM nor LIF induced COX-2 mRNA, suggesti ng that COX-2 might be implicated in the angiogenic activity of OSM, This w as confirmed by the inhibiting effect on OSM-induced HMEC-1 proliferation o f specific COX-2 inhibitors, In vivo studies confirmed this findings. We co nclude that induction of COX-2 by OSM is necessary for its angiogenic activ ity, but is not sufficient since IL-1 beta, which also induces COX-2 in HME C-1, has only a poor proliferative effect. (C) 1999 Federation of European Biochemical Societies.