In addition, the AS group displayed the highest protein levels of TXNIP, NLRP3, ASC, caspase-1, IL-1β, and IL-18, while the levels of these proteins in the AS + H <sub>2</sub> S group were higher than those in the sham group.
Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels.
Moreover, the use of loss- or gain-of-function genetically modified, atherosclerosis-prone mice has provided strong experimental evidence for a causal role of innate and adaptive immunity in atherosclerosis and has revealed the pathogenic activity of proinflammatory cytokines, including TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, and IL-18, and the atheroprotective effect of anti-inflammatory cytokines, including IL-10 and TGF-β.
Collectively, our results demonstrate that the coexpression and regulation of IL-18 and EMMPRIN in the vessel wall may amplify the inflammatory cascade and promote atherosclerosis and remodeling.
Increased plasma levels of IL-1β and IL-18, aggravated macrophage infiltration into atherosclerotic lesions, and accelerated development of atherosclerosis were detected in HHcy mice as compared with control mice, and were associated with the activation of NLRP3 inflammasomes.
The level of IL-17 and IL-18 in the atherosclerosis and disease control groups was higher than that in the healthy control group, and the level of IL-17 and IL-18 in the atherosclerosis was higher than that in the disease control group.
Therefore, in order to investigate IL-18 contribution to the immuno-inflammatory processes underlying atherosclerosis, a systems approach has been used in our studies.
Furthermore, we demonstrated the expression of IL-18BP in atherosclerotic lesions in a rhesus model of atherosclerosis, underscoring the need to fully understand the role of this protein as a primary negative regulator of IL-18 in multiple disease processes.
Atorvastatin inhibits IL-18-mediated aortic SMC migration and has therapeutic potential for attenuating the progression of atherosclerosis and restenosis.
It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability.
Variations of the IL18 gene consistently influence circulating levels of IL-18 and clinical outcome in patients with coronary artery disease, which supports the hypothesis of a causal role of IL-18 in atherosclerosis and its complications.
Activation of macrophage inflammasomes leads to interleukin (IL)-1β and IL-18 secretion and promotes atherosclerosis and its complications in mice and humans.
In this article, we aimed to present an updated review on these aspects regarding the contribution of IL-18 to important diseases such as cancer, autoimmunity, and inflammatory-mediated conditions including allergic diseases, metabolic syndrome, and atherosclerosis.
Because both IL-18 and Angiotensin II (Ang II) are implicated in atherosclerosis, our objective was to analyze the role of IL-18 signaling and potential cross-talk with Ang II in VSMC.
To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR.