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


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.
Center for Molecular Medicine and the Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Dirk M
DM
Wuttge
Xinghua
X
Zhou
Yuri
Y
Sheikine
Dick
D
Wågsäter
Veronika
V
Stemme
Ulf
U
Hedin
Sten
S
Stemme
Göran K
GK
Hansson
Allan
A
Sirsjö
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D001057:Apolipoproteins E; C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011991:Receptors, Virus; C099252:oxidized low density lipoprotein; D007371:Interferon-gamma; D002784:Cholesterol