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.
Iwasaki
Shiho
S
Department of Pediatrics, Yokohama City University, Yokohama 236-0004, Japan.
Minamisawa
Susumu
S
Yokoyama
Utako
U
Akaike
Toru
T
Quan
Hong
H
Nagashima
Yoji
Y
Nishimaki
Shigeru
S
Ishikawa
Yoshihiro
Y
Yokota
Shumpei
S
D000527:Alprostadil / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000196:embryology / Q000378:metabolism*; D000077214:Becaplermin; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004373:Ductus Arteriosus / Q000196:embryology / Q000378:metabolism*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D006820:Hyaluronic Acid / Q000378:metabolism*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019707:Receptors, Chemokine / Q000378:metabolism; D053647:Receptors, Interleukin-15 / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype
D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D019409:Interleukin-15; D008565:Membrane Proteins; D008738:Methyl Ethers; C461399:ONO-AE1-329; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C545652:Ptger4 protein, rat; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D053647:Receptors, Interleukin-15; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000077214:Becaplermin; D006820:Hyaluronic Acid; D000527:Alprostadil