Release of GM-CSF and G-CSF by human arterial and venous smooth muscle cells: differential regulation by COX-2

In addition to their traditional contractile function, vascular smooth musc le cells can be stimulated under inflammatory conditions to release a range of potent biological mediators. Indeed, we and others have shown that huma n vascular smooth muscle release the colony stimulating factors (CSF) granu locyte macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF) as well as large amounts of prostaglandins following the induction of cyclo-oxygenase-2 (CO X-2), when stimulated with cytokines. Here we demonstrate, for the first ti me, that co-induced COX-2 activity simultaneously suppresses GM-CSF release and potentiates G-CSF release by human vascular cells. Moreover, the diffe rential regulation of GM-CSF and G-CSF release by COX-2 was mimicked by the prostacyclin (PGI(2)) mimetic, cicaprost. These observations suggest that PGI(2), released following the induction of COX-2, differentially regulates the release of GM-CSF (suppresses) and G-CSF (potentiates) from human vasc ular cells.