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CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2004 Apr; Vol. 24 (4), pp. 750-5. Date of Electronic Publication: 2004 Feb 26. - Publication Year :
- 2004
-
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.<br />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.<br />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.
- Subjects :
- Animals
Apolipoproteins E deficiency
Apolipoproteins E genetics
Arteriosclerosis genetics
Arteriosclerosis metabolism
Carotid Artery Diseases immunology
Cell Line
Chemokine CXCL16
Chemokine CXCL6
Chemokines, CXC biosynthesis
Chemokines, CXC genetics
Chemotaxis, Leukocyte drug effects
Cholesterol metabolism
Female
Humans
Interferon-gamma pharmacology
Lipoproteins, LDL metabolism
Membrane Proteins biosynthesis
Membrane Proteins genetics
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, Scavenger
Receptors, Virus biosynthesis
Receptors, Virus genetics
T-Lymphocytes drug effects
Up-Regulation drug effects
Carotid Artery Diseases metabolism
Chemokines, CXC physiology
Foam Cells metabolism
Interferon-gamma physiology
Membrane Proteins physiology
Receptors, Immunologic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 14988089
- Full Text :
- https://doi.org/10.1161/01.ATV.0000124102.11472.36