Autocrine role of vascular IL-15 in intimal thickening.
Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor alpha expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling.
Cercek
Miha
M
Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center/David Geffen School of Medicine at UCLA, USA.
Matsumoto
Michiaki
M
Li
Hongyan
H
Chyu
Kuang-Yuh
KY
Peter
Ashok
A
Shah
Prediman K
PK
Dimayuga
Paul C
PC
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology; D002339:Carotid Arteries / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism*
D000906:Antibodies; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D008565:Membrane Proteins; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D023062:Receptors, Interleukin-8A