Autocrine role of vascular IL-15 in intimal thickening.

Abstract

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.

• Authors: Miha Cercek, Michiaki Matsumoto, Hongyan Li, Kuang-Yuh Chyu, Ashok Peter, Prediman K Shah, Paul C Dimayuga
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 339 Issue 2 Pg. 618-23 (Jan 13 2006) ISSN: 0006-291X [Print] United States
• PMID: 16321364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• CX3CL1 protein, human
• Chemokine CX3CL1
• Chemokines, CX3C
• Cx3cl1 protein, mouse
• IL15RA protein, human
• Il15ra protein, mouse
• Interleukin-15
• Membrane Proteins
• Receptors, Interleukin-15
• Receptors, Interleukin-2
• Receptors, Interleukin-8A

Topics

• Animals
• Antibodies (pharmacology)
• Autocrine Communication (drug effects)
• B-Lymphocytes (cytology)
• Carotid Arteries (metabolism)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Chemokine CX3CL1
• Chemokines, CX3C (metabolism)
• Gene Expression Regulation (drug effects)
• Interleukin-15 (antagonists & inhibitors, genetics, metabolism, pharmacology)
• Lymphocyte Count
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocytes, Smooth Muscle (cytology, drug effects)
• Receptors, Interleukin-15
• Receptors, Interleukin-2 (genetics, metabolism)
• Receptors, Interleukin-8A (metabolism)
• T-Lymphocytes (cytology)
• Tunica Intima (drug effects, metabolism)