Abstract
Inflammatory cytokines are well-recognized mediators of atherosclerosis. Depending on the pathological context, type I interferons (IFNs; IFNalpha and IFNbeta) exert either pro- or anti-inflammatory immune functions, but their exact role in atherogenesis has not been clarified. Here, we demonstrate that IFNbeta enhances macrophage-endothelial cell adhesion and promotes leukocyte attraction to atherosclerosis-prone sites in mice in a chemokine-dependent manner. Moreover, IFNbeta treatment accelerates lesion formation in two different mouse models of atherosclerosis and increases macrophage accumulation in the plaques. Concomitantly, absence of endogenous type I IFN signaling in myeloid cells inhibits lesion development, protects against lesional accumulation of macrophages, and prevents necrotic core formation. Finally, we show that type I IFN signaling is upregulated in ruptured human atherosclerotic plaques. Hereby, we identify type I IFNs as proatherosclerotic cytokines that may serve as additional targets for prevention or treatment.
Original language | English |
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Pages (from-to) | 142-153 |
Number of pages | 12 |
Journal | Cell Metabolism |
Volume | 12 |
Issue number | 2 |
DOIs | |
Publication status | Published - 4 Aug 2010 |
Keywords
- SYSTEMIC-LUPUS-ERYTHEMATOSUS
- APOLIPOPROTEIN-E-DEFICIENT
- MULTIPLE-SCLEROSIS
- DENDRITIC CELLS
- CROSS-TALK
- MICE
- BETA
- CHEMOKINES
- APOPTOSIS
- SUSCEPTIBILITY