Activation of NLRP3 inflammasome assembly is associated with smoking status of patients with coronary artery disease.,International Immunopharmacology

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Activation of NLRP3 inflammasome assembly is associated with smoking status of patients with coronary artery disease.
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-07-22 , DOI: 10.1016/j.intimp.2020.106820
Sakshi Mehta ₁ , Rajesh Vijayvergiya ₂ , Veena Dhawan ₁

Affiliation

Objective

Cigarette smoke is considered as a sterile inflammatory stimulus which triggers an innate immune response, accountable for vascular events. Previously, we reported smoking-induced NLRP3 inflammasome activation in the pathogenesis of atherosclerosis through caspase-1 activation and secretion of pro-cytokines (interleukin (IL)-1β and IL-18) in vitro and in vivo. Therefore, the present study aimed to reconnoitre the association of cigarette smoking and NLRP3 inflammasome activation ex vivo in human subjects with coronary atherosclerosis.

Methods and Results

In order to establish and validate the association between smoking status and NLRP3 inflammasome ex vivo, mononuclear cells were isolated from smokers with angiographically-proven coronary artery disease (CAD); non-smokers with CAD; smokers without CAD, and healthy non-smokers (controls) (n = 20 each). The transcriptional and translational expression of NLRP3 inflammasome markers i.e. NLRP3, pro-caspase-1, caspase-1, pro-IL-1β, IL-1β, pro-IL-18 and IL-18 was significantly increased (2 to 7-fold) in smokers with CAD vs non-smokers with CAD; and smokers without CAD vs non-smoker controls. In addition, the oxidative stress, an upstream mediator of NLRP3 inflammasome was evaluated and found to be significantly augmented in smokers vs non-smokers (with and without CAD respectively). Further, the levels of serum cotinine, oxidative stress markers (8-isoprostane and 8-oxo-2́′-deoxyguanosine), caspase-1 and pro-cytokines (IL-1β and IL-18) were also higher in smokers vs non-smokers. Moreover, the levels of pro-cytokines were positively correlated with caspase-1 and serum cotinine, corroborating the secretion of cytokines in a caspase-1-dependent manner.

Conclusion

Our data may imply NLRP3 inflammasome as a mediator of the pro-atherosclerotic property of cigarette smoking in atherosclerotic patients.

中文翻译：

NLRP3炎性小体组装的激活与冠心病患者的吸烟状态有关。

目的

香烟烟雾被认为是一种无菌的炎症刺激，它会触发先天性免疫反应，这是血管事件的原因。以前，我们报道了在体外和体内， caspase-1激活和促细胞因子（白介素（IL）-1β和IL-18）的分泌，在动脉粥样硬化的发病机理中吸烟诱导的NLRP3炎性体激活。因此，本研究旨在证实吸烟与冠状动脉粥样硬化人类受试者离体的NLRP3炎性体激活的关联。

方法与结果

为了建立和验证吸烟状况与离体NLRP3炎性小体之间的关联，从具有血管造影证实的冠状动脉疾病（CAD）的吸烟者中分离出单核细胞。有CAD的非吸烟者; 没有CAD的吸烟者和健康的非吸烟者（对照组）（每人n = 20）。NLRP3炎性小体标记（即NLRP3，caspase-1，caspase-1，IL-1β，IL-1β，IL-18和IL-18）的转录和翻译表达显着增加（2至7倍））与CAD吸烟者VS非吸烟者与CAD; 以及没有CAD的吸烟者与非吸烟者的对照。此外，对氧化应激（NLRP3炎性小体的上游介质）进行了评估，发现吸烟者与非吸烟者（分别使用CAD和不使用CAD）。此外，血清可替宁，氧化应激标记物（8-异前列烷和8-氧代-2'-脱氧鸟苷），胱天蛋白酶-1和促细胞因子（IL-1β和IL-18）的水平也较高吸烟者VS非吸烟者。此外，前细胞因子的水平与caspase-1和血清可替宁呈正相关，以caspase-1依赖性的方式证实了细胞因子的分泌。