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Arthritis Rheum. 2011 Feb;63(2):492-502. doi: 10.1002/art.30165.

Interferon-α priming promotes lipid uptake and macrophage-derived foam cell formation: a novel link between interferon-α and atherosclerosis in lupus.

Author information

1
Shanghai Institute of Rheumatology, Renji Hospital, Molecular Rheumatology Laboratory of Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai JiaoTong University School of Medicine, Shanghai, China.

Abstract

OBJECTIVE:

An increased risk of premature atherosclerosis has been associated with systemic lupus erythematosus (SLE), and type I interferon (IFN) has been shown to play a pathogenic role in human SLE. The aim of this study was to determine whether IFNα is involved in the development of atherosclerosis in patients with SLE by promoting lipid uptake and macrophage-derived foam cell formation, which is a crucial step in early atherosclerosis.

METHODS:

The effects of IFNα on lipid uptake and foam cell formation were determined by flow cytometry and oil red O staining. Messenger RNA and protein expression of scavenger receptors (SRs) was examined. Promoter activity was detected by luciferase reporter assay. Expression of macrophage SR class A (SR-A) and IFN-inducible genes (IFIGs) was measured in peripheral blood mononuclear cells obtained from 42 patients with SLE and 42 healthy donors.

RESULTS:

IFNα priming increased the uptake of oxidized low-density lipoprotein and hence enhanced foam cell formation by up-regulating SR-A expression. IFNα increased SR-A expression via enhancing its promoter activities. Examination using signaling inhibitors revealed that a phosphatidylinositol 3-kinase/Akt signaling pathway appeared to be involved in this process. Notably, SR-A messenger RNA was significantly increased in patients with SLE compared to normal subjects and positively correlated with IFIG expression.

CONCLUSION:

Our data suggest that IFNα priming up-regulated the expression of SR-A in human monocyte/macrophages, leading to increased lipid uptake and foam cell formation. Activation of the IFN signaling pathway may be linked to the risk of atherosclerosis by affecting plaque formation in patients with SLE. These findings provide novel insights into the mechanisms of and potential therapeutic approaches to premature atherosclerosis in patients with SLE.

PMID:
21280004
DOI:
10.1002/art.30165
[Indexed for MEDLINE]
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