5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.
5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.
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5-羟甲基糠醛通过抑制内质网应激和 NLRP3 炎症小体激活减轻炎症性肺损伤
DOI：
10.3389/fcell.2021.782427
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发表时间：
2021
影响因子：
5.5
通讯作者：
Xie T
中科院分区：
文献类型：
--
作者：
Zhang H;Jiang Z;Shen C;Zou H;Zhang Z;Wang K;Bai R;Kang Y;Ye XY;Xie T
5-羟甲基糠醛(5-HMF)是多种食品和中药制剂热加工过程中常见的反应产物。本研究旨在探讨5-HMF对内毒素诱导的急性肺损伤(ALI)的保护作用及其机制。我们的研究结果表明，5-HMF通过减轻肺泡破坏、中性粒细胞浸润和炎性细胞因子的释放而减轻脂多糖(LPS)诱导的小鼠ALI。此外，5-羟甲基呋喃可通过抑制NF-κB信号通路、炎性小体激活和内质网应激，在体外显著抑制巨噬细胞和单核细胞对内毒素的反应。ATF4或CHOP的过度表达逆转了5-HMF对NLRP3炎症小体的抑制作用，提示内质网应激参与了5-HMF对NLRP3炎症小体介导的炎症的负性调节。与此一致的是，5-HMF对体内肺功能障碍的改善作用可被内质网应激诱导剂衣霉素逆转。综上所述，我们的研究结果阐明了5-HMF对内毒素诱导的急性肺损伤的抗炎和保护作用，并揭示了其通过抑制内质网应激来对抗NLRP3炎症性疾病的关键机制。
5-Hydroxymethylfurfural (5-HMF) is a common reaction product during heat processing and the preparation of many types of foods and Traditional Chinese Medicine formulations. The aim of this study was to evaluate the protective effect of 5-HMF on endotoxin-induced acute lung injury (ALI) and the underlying mechanisms. Our findings indicate that 5-HMF attenuated lipopolysaccharide (LPS)-induced ALI in mice by mitigating alveolar destruction, neutrophil infiltration and the release of inflammatory cytokines. Furthermore, the activation of macrophages and human monocytes in response to LPS was remarkably suppressed by 5-HMF in vitro through inhibiting the NF-κB signaling pathway, NLRP3 inflammasome activation and endoplasmic reticulum (ER) stress. The inhibitory effect of 5-HMF on NLRP3 inflammasome was reversed by overexpressing ATF4 or CHOP, indicating the involvement of ER stress in the negative regulation of 5-HMF on NLRP3 inflammasome-mediated inflammation. Consistent with this, the ameliorative effect of 5-HMF on in vivo pulmonary dysfunction were reversed by the ER stress inducer tunicamycin. In conclusion, our findings elucidate the anti-inflammatory and protective efficacy of 5-HMF in LPS-induced acute lung injury, and also demonstrate the key mechanism of its action against NLRP3 inflammasome-related inflammatory disorders via the inhibition of ER stress.
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