Abstract
AimInterleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in vitro.MethodsPlasma IL-27 was measured by enzyme immunoassay in patients with carotid stenosis (n = 140) and in healthy controls (n = 19). Expression of IL-27 and IL-27R was analyzed by quantitative PCR and immunohistochemistry in plaques from patients and in non-atherosclerotic vessels. THP-1 monocytes, primary monocytes and peripheral blood mononuclear cells (PBMCs) were used to study effects of IL-27 in vitro.ResultsOur main findings were: (i) Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. (ii) Gene expression of IL-27 and IL-27R was significantly elevated in plaques compared to control vessels, and co-localized to macrophages. (iii) In vitro, IL-27 increased NLRP3 inflammasome activation in monocytes with enhanced release of IL-1 β.ConclusionsWe demonstrate increased levels of IL-27 and IL-27R in patients with carotid atherosclerosis. Our in vitro findings suggest an inflammatory role for IL-27, which can possibly be linked to atherosclerotic disease development.
Highlights
Atherosclerosis is a progressive disorder in which lipids, immune cells and vascular cells accumulate in the arterial wall, leading to development of an atherosclerotic plaque
Our main findings were: (i) Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. (ii) Gene expression of IL-27 and IL-27R was significantly elevated in plaques compared to control vessels, and co-localized to macrophages. (iii) In vitro, IL-27 increased NLRP3 inflammasome activation in monocytes with enhanced release of IL-1 β
We demonstrate increased levels of IL-27 and IL-27R in patients with carotid atherosclerosis
Summary
Atherosclerosis is a progressive disorder in which lipids, immune cells and vascular cells accumulate in the arterial wall, leading to development of an atherosclerotic plaque. In vitro data illustrate anti-atherogenic effects of IL-27 on efflux of cholesterol from macrophages, whereas pro-atherogenic effects of IL-27 in endothelial activation and early plaque development have been shown [19,20,21]. Together these findings point to a potential role for IL-27 in atherogenesis, but the mechanisms of action as well as the net effect of this cytokine in atherosclerosis is far from clear. Data on IL-27 expression in clinical atherosclerosis are scarce
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