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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Dirk Wuttge
  • Xinghua Zhou
  • Yuri Sheikine
  • Dick Wagsater
  • Veronika Stemme
  • Ulf Hedin
  • Sten Stemme
  • Goran K Hansson
  • Allan Sirsjo
Externa organisationer
  • Karolinska University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)750
TidskriftArteriosclerosis, Thrombosis and Vascular Biology
Volym24
Utgåva nummer4
StatusPublished - 2004
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa