Autocrine role of vascular IL-15 in intimal thickening

Biochem Biophys Res Commun. 2006 Jan 13;339(2):618-23. doi: 10.1016/j.bbrc.2005.11.050. Epub 2005 Nov 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Interleukin-15 / pharmacology*
  • Lymphocyte Count
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-8A / metabolism
  • T-Lymphocytes / cytology
  • Tunica Intima / drug effects*
  • Tunica Intima / metabolism*

Substances

  • 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