Interleukin‐36 receptor antagonist attenuates atherosclerosis development by inhibiting NLRP3 inflammasome

Tian, Yuan; Ling, Xue-Yan; Chen, Danling; Zhang, Xiuqiong; Qiu, Chuan-mei

doi:10.1002/jcp.29813

Cited by 15 publications

(9 citation statements)

References 14 publications

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“…In atherosclerosis, macrophages play a central role in the initiation, growth, and final rupture of arterial plaque. Various studies based on different purposes have fully proved the vital role of macrophage inflammasome activation in the pathogenesis of atherosclerosis ( Tang et al, 2019 ; Yin et al, 2019 ; Tian et al, 2020 ; Wang et al, 2020 ). NLRP3 inflammasome activation is considered to be a key catalyst for atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

α1-nAchR-Mediated Signaling Through Lipid Raft Is Required for Nicotine-Induced NLRP3 Inflammasome Activation and Nicotine-Accelerated Atherosclerosis

Fu-jian

Zeng

Liu

et al. 2021

Front. Cell Dev. Biol.

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BackgroundNicotine exerts direct effects on multiple cell types in the cardiovascular system by associating with its high-affinity nicotinic acetylcholine receptors (nAchRs). Lipid raft is a membrane microdomain that recruits various receptors and signaling molecules for coordinating cellular immune response and many others signaling processes. Here, we aim to identify the essential role of lipid raft in mediating nicotine-triggered inflammatory and nicotine-accelerated atherosclerosis, and to figure out the specific receptor of nicotine-induced Nod-like receptor protein 3 (NLRP3) inflammasome activation in macrophage.Methods and ResultsApoE–/– mice were fed with a high-fat diet to build atherosclerosis model. Methyl-β-cyclodextrin was used to interrupt intact lipid raft. We confirmed that nicotine triggered NLRP3 inflammasome activation and induced macrophage migration into atherosclerotic plaque, thus accelerated atherosclerosis in apoE–/– mice fed with a high-fat diet. Mechanically, nicotine increased the expression of α1-nAChR and stimulated the accumulation of α1-nAChR in lipid raft, leading to NLRP3 inflammasome activation in macrophage. Conversely, silencing of α1-nAChR in macrophage sufficiently blocked the pro-inflammasome activation effect of nicotine, indicating that α1-nAChR was the specific receptor for nicotine in triggering NLRP3 inflammasome in macrophage. Furthermore, both the destruction of lipid raft by methyl-β-cyclodextrin and the interference of lipid raft clustering by silencing acid sphingomyelinase reversed nicotine-induced NLRP3 inflammasome activation by reducing the accumulation of α1-nAChR in lipid raft in macrophage, suggesting lipid raft–mediated accumulation of α1-nAChR was the key event in regulating the pro-inflammatory effects of nicotine in macrophage. Importantly, nicotine-induced NLRP3 inflammasome activation and macrophage migration into atherosclerotic plaque were reversed by methyl-β-cyclodextrin, making a significant improvement for atherosclerosis in apoE–/– mice fed with a high-fat diet.Conclusionα1-nAChR-mediated signaling through lipid raft is required for NLRP3 inflammasome activation and pro-atherosclerotic property of nicotine.

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Section: Introductionmentioning

confidence: 99%

α1-nAchR-Mediated Signaling Through Lipid Raft Is Required for Nicotine-Induced NLRP3 Inflammasome Activation and Nicotine-Accelerated Atherosclerosis

Fu-jian

Zeng

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…IL-36 cytokines promote NLRP3 activation and IL-23/IL-17 production, leading to kidney inflammation and fibrosis ( 44 ). Another study revealed that IL-36Ra protects from atherosclerosis by inhibiting NLRP3 activation, and IL-1β and caspase-1 p10 production ( 45 ). The level of NLRP3 activation increased in NA patients ( 119 ), and this was associated with the degree of neutrophil airway inflammation, disease severity, and steroid resistance in asthma patients ( 120 ).…”

Section: Il-36 In Human Asthmamentioning

confidence: 99%

“…A complex relationship exists among IL-36 cytokines, nod-like receptor family pyrin domain 3 (NLRP3), neutrophil extracellular traps (NETs) and autophagy. In vivo and in vitro experiments have demonstrated that IL-36α promotes the NLRP3 expression and activation in mouse renal tubular epithelial cells and macrophages ( 44 ), while IL-36Ra inhibits NLRP3 activation and reduces inflammation in a mouse model of atherosclerosis ( 45 ). NETs increase the expression of IL-36α and IL-36γ in human bronchial epithelial cells ( 46 ).…”

Section: Introductionmentioning

confidence: 99%

IL-36 Cytokines: Their Roles in Asthma and Potential as a Therapeutic

Dong

Hao

et al. 2022

Front. Immunol.

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Interleukin (IL)-36 cytokines are members of the IL-1 superfamily, which consists of three agonists (IL-36α, IL-36β and IL-36γ) and an IL-36 receptor antagonist (IL-36Ra). IL-36 cytokines are crucial for immune and inflammatory responses. Abnormal levels of IL-36 cytokine expression are involved in the pathogenesis of inflammation, autoimmunity, allergy and cancer. The present study provides a summary of recent reports on IL-36 cytokines that participate in the pathogenesis of inflammatory diseases, and the potential mechanisms underlying their roles in asthma. Abnormal levels of IL-36 cytokines are associated with the pathogenesis of different types of asthma through the regulation of the functions of different types of cells. Considering the important role of IL-36 cytokines in asthma, these may become a potential therapeutic target for asthma treatment. However, existing evidence is insufficient to fully elucidate the specific mechanism underlying the action of IL-36 cytokines during the pathological process of asthma. The possible mechanisms and functions of IL-36 cytokines in different types of asthma require further studies.

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“…Finally, interleukins are a family of cytokines strongly associated with chronic inflammation and atherogenesis. Some interleukins can have proatherogenic effects while fewer interleukins can have atheroprotective effects [197,[203][204][205][206][207][208]. These DNA methylation alterations in pathways associated with atherogenesis suggest a usefulness for DNA methylation based CVD biomarkers.…”

Section: Functional Analysis Of Differentially Methylated Genes In Cvdmentioning

confidence: 99%

Radiation-induced cardiovascular disease: an overlooked role for DNA methylation?

et al. 2021

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Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly prominent among patients receiving mediastinal radiotherapy, such as breast cancer and Hodgkin's lymphoma patients. A number of mechanisms of radiation-induced CVD pathogenesis have been proposed such as endothelial inflammatory activation, premature endothelial senescence, increased ROS and mitochondrial dysfunction. However, current research seems to point to a so-far unexamined and potentially novel involvement of epigenetics in radiation-induced CVD pathogenesis. Firstly, epigenetic mechanisms have been implicated in CVD pathophysiology. In addition, several studies have shown that ionizing radiation can cause epigenetic modifications, especially DNA methylation alterations. As a result, this review aims to provide a summary of the current literature linking DNA methylation to radiation-induced CVD and thereby explore DNA methylation as a possible contributor to radiation-induced CVD pathogenesis.

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Interleukin‐36 receptor antagonist attenuates atherosclerosis development by inhibiting NLRP3 inflammasome

Cited by 15 publications

References 14 publications

α1-nAchR-Mediated Signaling Through Lipid Raft Is Required for Nicotine-Induced NLRP3 Inflammasome Activation and Nicotine-Accelerated Atherosclerosis

α1-nAchR-Mediated Signaling Through Lipid Raft Is Required for Nicotine-Induced NLRP3 Inflammasome Activation and Nicotine-Accelerated Atherosclerosis

IL-36 Cytokines: Their Roles in Asthma and Potential as a Therapeutic

Radiation-induced cardiovascular disease: an overlooked role for DNA methylation?

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