Interleukin-15 inhibits smooth muscle cell proliferation and hyaluronan production in rat ductus arteriosus.

Neointimal cushion formation (NCF) is an important vascular remodeling for anatomical closure of the ductus arteriosus (DA). Inflammatory responses to vascular injury or atherosclerosis are known to be associated with the pathogenesis of NCF. We found that the expression of interleukin (IL)-15 mRNA was significantly higher in rat DA than in the aorta. IL-15 immunoreactivity was detected predominantly in the internal elastic laminae (IEL) and to a lesser extent in smooth muscle cells (SMCs) in rat DA. Prostaglandin E (PGE) increased the expression of IL-15 mRNA in cultured DA SMCs. IL-15 significantly attenuated the platelet-derived growth factor (PDGF)-BB-mediated SMC proliferation, but did not change SMC migration. IL-15 significantly attenuated PGE1-induced hyaluronic acid (HA) production in a dose-dependent manner, which is a potent stimulator of NCF. Accordingly, IL-15 might have an inhibitory effect on the physiologic vascular remodeling processes in closing the DA.