College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), Ministry of Agriculture, Shanghai, 201306, China.
School of Food Science and Technology, Jiangnan University, Wuxi, China.
Food Chem Toxicol. 2022 Oct;168:113400. doi: 10.1016/j.fct.2022.113400. Epub 2022 Aug 31.
Exposure to acrolein, one environmental and dietary pollutant, has been shown to cause inflammation. Here, we reported for the first time that acrolein aggravated lipopolysaccharide (LPS)-induced inflammation in Human umbilical vein endothelial cells (HUVEC) as evidenced by the further increased mRNA expression of three pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Acrolein also further increased the generation of reactive oxygen species (ROS) and decreased the activity of glutathione peroxidase (GSH-Px) in LPS-pretreated HUVEC. Moreover, acrolein treatment further increased the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) expression, caspase-1 cleavage, and downstream matures interleukin 18 (IL-18) and IL-1β level in LPS-pretreated HUVEC. Acrolein treatment also further increased the expressions of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and phospho-NF-κB P65 (P-P65) in the LPS pre-treated HUVEC. Thus, acrolein aggravated LPS-induced HUVEC inflammation through induction of oxidative stress, and activation of NLRP3 inflammasome and HMGB1/MYD88/NF-κB signaling pathway. In addition, apigenin and apigenin-7, 4'-O-dioctanoate attenuated acrolein-aggravated inflammation by targeting the above signaling pathways. Our findings could help to develop potential therapeutic strategies against acrolein-enhanced inflammation.
丙烯醛是一种环境和饮食污染物，已被证实会引起炎症。在这里，我们首次报道丙烯醛加剧了脂多糖（LPS）诱导的人脐静脉内皮细胞（HUVEC）炎症，其证据为三种促炎细胞因子（包括白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的 mRNA 表达进一步增加。丙烯醛还进一步增加了 LPS 预处理的 HUVEC 中活性氧（ROS）的产生，并降低了谷胱甘肽过氧化物酶（GSH-Px）的活性。此外，丙烯醛处理还进一步增加了核苷酸寡聚化结构域样受体蛋白 3（NLRP3）和凋亡相关斑点样蛋白含半胱氨酸蛋白酶募集结构域（ASC）的表达、半胱天冬酶-1 的切割以及下游成熟白细胞介素 18（IL-18）和 IL-1β的水平在 LPS 预处理的 HUVEC 中。丙烯醛处理还进一步增加了高迁移率族蛋白 B1（HMGB1）、Toll 样受体 4（TLR4）、髓样分化因子 88（MyD88）和磷酸化核因子-κB P65（P-P65）在 LPS 预处理的 HUVEC 中的表达。因此，丙烯醛通过诱导氧化应激、激活 NLRP3 炎性小体和 HMGB1/MYD88/NF-κB 信号通路，加剧了 LPS 诱导的 HUVEC 炎症。此外，芹菜素和芹菜素-7,4'-O-二辛酯通过靶向上述信号通路，减轻了丙烯醛加剧的炎症。我们的研究结果可能有助于开发针对丙烯醛增强炎症的潜在治疗策略。
