CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions

Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):750-5. doi: 10.1161/01.ATV.0000124102.11472.36. Epub 2004 Feb 26.

Abstract

Objective: Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-gamma (IFN-gamma)-cytokine abundant in atherosclerotic lesions.

Methods and results: CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN-gamma induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN-gamma induced CXCL16 expression in murine atherosclerotic lesions.

Conclusions: We demonstrate a novel role of IFN-gamma in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Arteriosclerosis / genetics
  • Arteriosclerosis / metabolism
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / metabolism*
  • Cell Line
  • Chemokine CXCL16
  • Chemokine CXCL6
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / genetics
  • Chemokines, CXC / physiology*
  • Chemotaxis, Leukocyte / drug effects
  • Cholesterol / metabolism
  • Female
  • Foam Cells / metabolism*
  • Humans
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Lipoproteins, LDL / metabolism
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Monocytes / drug effects
  • Monocytes / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, CXCR
  • Receptors, CXCR6
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / genetics
  • Receptors, Cytokine / biosynthesis
  • Receptors, Cytokine / genetics
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Receptors, Scavenger
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / genetics
  • T-Lymphocytes / drug effects
  • Up-Regulation / drug effects

Substances

  • Apolipoproteins E
  • CXCL16 protein, human
  • CXCR6 protein, human
  • Chemokine CXCL16
  • Chemokine CXCL6
  • Chemokines, CXC
  • Cxcl16 protein, mouse
  • Cxcr6 protein, mouse
  • Lipoproteins, LDL
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, CXCR
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, G-Protein-Coupled
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Receptors, Virus
  • oxidized low density lipoprotein
  • Interferon-gamma
  • Cholesterol