Reactive oxygen species‐mediated activation of NLRP3 inflammasome associated with pyroptosis in Het‐1A cells induced by the co‐exposure of nitrosamines
Reactive oxygen species‐mediated activation of NLRP3 inflammasome associated with pyroptosis in Het‐1A cells induced by the co‐exposure of nitrosamines
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活性氧介导的 NLRP3 炎症小体激活与同时接触亚硝胺诱导的 Het-1A 细胞焦亡相关
DOI：
10.1002/jat.4332
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发表时间：
2022-04
影响因子：
3.3
通讯作者：
Lihong Yin
中科院分区：
文献类型：
--
作者：
Qiwei Liu;Chao Zhao;Jingjing Zhou;Hu Zhang;Lihong Yin;Shizhi Wang;Yuepu Pu;Lihong Yin
亚硝胺是一类与消化道肿瘤相关的重要环境致癌物。炎症反应作为亚硝胺的早期毒性作用，参与了细胞的恶性转化，促进了肿瘤的发生和发展。然而，NLRP 3炎性体在亚硝胺诱导的炎症反应中的作用尚不清楚。在这项研究中，人食管上皮细胞（Het-1A）被用来探讨NLRP 3炎性体的激活下共同暴露于饮用水中常见的9种亚硝胺在0，4，20，100，500和2500 ng/mL的剂量下的潜在机制。结果表明，亚硝胺刺激NLRP 3炎性体的激活，并以剂量依赖性方式诱导细胞氧化损伤。活性氧清除剂N-乙酰-L-半胱氨酸（NAC），特别是线粒体活性氧（mtROS）清除剂Mito-TEMPO预处理，可有效抑制NLRP 3炎性体的激活，提示亚硝胺可通过mtROS介导NLRP 3炎性体的激活。此外，通过加入caspase-1抑制剂Z-YVAD-FMK和构建NLRP 3下调的Het-1A细胞系，我们发现亚硝胺共暴露也通过NLRP 3/caspase-1/GSDMD途径促进细胞的焦亡。本研究揭示了亚硝胺联合暴露引发NLRP 3炎性小体激活的潜在机制，为亚硝胺的毒性作用提供了新的视角。
Nitrosamines were a class of important environmental carcinogens associated with digestive tract neoplasms. As the early toxic effect of nitrosamines, inflammatory response participated in the malignant transformation of cells and promoted the occurrence and development of tumors. However, the role of NLRP3 inflammasome in the nitrosamines-induced inflammatory response was unclear. In this study, the human esophageal epithelial cells (Het-1A) were used to explore potential mechanisms of the activation of NLRP3 inflammasome under co-exposure to nine nitrosamines commonly found in drinking water at the doses of 0, 4, 20, 100, 500, and 2500 ng/mL. The results showed that nitrosamines stimulated activation of the NLRP3 inflammasome and induced cellular oxidative damage in a dose-dependent manner. Pretreatment of reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), particularly mitochondrial reactive oxygen species (mtROS) scavengers Mito-TEMPO, effectively inhibited the activation of NLRP3 inflammasome, suggesting that nitrosamines could mediate the activation of NLRP3 inflammasome via mtROS. Furthermore, we found that nitrosamines co-exposure also promoted cell pyroptosis through the NLRP3/caspase-1/GSDMD pathway, which was demonstrated by adding the caspase-1 inhibitor Z-YVAD-FMK and constructing NLRP3 downregulated Het-1A cell line. This study revealed the underlying mechanism of the activation of NLRP3 inflammasome initiated by nitrosamines co-exposure and provided new perspectives on the toxic effects of nitrosamines.
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影响因子：
3.6
作者：
Adeleke, Gbadebo E.;Adaramoye, Oluwatosin A.
通讯作者：
Adaramoye, Oluwatosin A.
影响因子：
8
作者：
通讯作者：
--
影响因子：
8.7
作者：
Horvath GL;Schrum JE;De Nardo CM;Latz E
通讯作者：
Latz E
影响因子：
8.7
作者：
Elliott EI;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
25.7
作者：
Woolbright BL;Jaeschke H
通讯作者：
Jaeschke H