Protective effect of the polarity of macrophages regulated by IL-37 on atherosclerosis

Abstract

ABSTRACT.As an anti-inflammatory cytokine, interleukin-37 (IL-37) provides certain protective effects against inflammatory and autoimmune diseases. Recent reports indicate that IL-37 is expressed in foam cells of atherosclerotic plaques in both the coronary and carotid arteries of humans, suggesting the possible involvement of IL-37 in the pathogenesis and progression of atherosclerosis. Current evidence supports the protective role that IL-37 plays against atherosclerosis via the regulation of different subtypes of macrophage. Atherosclerosis was induced in apolipoprotein E -/-mice through diet, and the mice were then given IL-37 to observe patterns in the aorta plaque. Furthermore, human peripheral blood-derived monocytes were cultured for seven days to induce the differentiation of macrophages. Specifically, we observed the effect of IL-37 on oxygenated low density lipoprotein (ox-LDL)-induced macrophage polarity, in addition to conducting an expressional assay of the M1 cell markers tumor necrosis factor (TNF)-α and CD86 and the M2 marker CD206. IL-37 effectively decreased the area ratio between the aorta plaque and vascular cavity. We also observed that M1 macrophages can be induced from peripheral monocytes by ox-LDL, with significant elevation of marker molecules TNF-α and CD86. The co-stimulation of IL-37 and ox-LDL, however, inhibited the induction of M1 cells and facilitated the transformation of macrophages into M2 cells, as supported by the elevation of cellspecific marker CD206. These results indicate that IL-37 can prevent atherosclerosis by modulating macrophage polarity.

Macrophage-Specific Expression of IL-37 in Hyperlipidemic Mice Attenuates Atherosclerosis

“…Because macrophages are central to disease pathogenesis in various ways from the early to late stages of atherosclerosis, they provide a valuable delivery system for expression of anti-inflammatory mediators, such as IL-37, to alter the plaque microenvironment (19). The anti-inflammatory benefits of IL-37 have been widely accepted, and its potential as a therapeutic measure for reducing the pathogenesis of atherosclerosis has been discussed (20), yet exploration of its effects on plaque development has been limited to systemic treatment with rIL-37 (21,22). The delivery of IL-37 directly to the plaque microenvironment via macrophage-specific expression has not been investigated.…”

Development and characterization of monoclonal antibody against human IL-37b

“…IL-37 is involved in the suppression of innate and adaptive immunity (Boraschi et al 2011;Chen and Fujita 2015;Ye et al 2014). Recent reports indicate that IL-37 plays important roles in inflammatory disease (Charrad et al 2016;Ye et al 2014;Zhao et al 2014b), infectious disease (Anuradha et al 2016;Hojen et al 2015;Samarani et al 2016), cancer (Ding et al 2016;Ge et al 2016) and angiocardiopathy (Huang et al 2016;Yu et al 2016). However, the exact mechanisms of IL-37 in human disease remain to be further studied.…”

The emerging role of interleukin‐37 in cardiovascular diseases

“…Boraschi et al found that IL‐37 was expressed in the foam‐like cells of atherosclerotic coronary and carotid artery plaques, suggesting that IL‐37 is associated with the activation of macrophages and the shift from macrophages to foam cells. Huang et al found IL‐37 effectively decreased the area ratio between the aorta plaque and vascular cavity. They also observed IL‐37 inhibited M1 macrophages induction from peripheral monocytes by ox‐LDL and facilitated the transformation of macrophages into M2 cells .…”

“…Huang et al found IL‐37 effectively decreased the area ratio between the aorta plaque and vascular cavity. They also observed IL‐37 inhibited M1 macrophages induction from peripheral monocytes by ox‐LDL and facilitated the transformation of macrophages into M2 cells . These results indicate that IL‐37 may prevent atherosclerosis by modulating macrophage polarity.…”

“…Atherosclerosis "M1!M2 # NF-kB, #ICAM-1 #Inflammatory cytokines #Calcification areas [26,28,38,39] Myocardial infarction "Tregs, #MPO, #ROS #Myocardial fibrosis #Cardiomyocyte apoptosis #Infarct size "Left ventricular function [17,44,46] Ischemia/reperfusion (I/R) #Inflammation "Tregs "FoxP3, and CTLA-4 #Cardiomyocyte apoptosis #Infarct size "Left ventricular function [60,61] IL-37 in cardiovascular diseases macrophages induction from peripheral monocytes by ox-LDL and facilitated the transformation of macrophages into M2 cells [28]. These results indicate that IL-37 may prevent atherosclerosis by modulating macrophage polarity.…”