Dataset Information

5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

ABSTRACT: 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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC8711100 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

Zhang Hang H Jiang Zheyi Z Shen Chuanbin C Zou Han H Zhang Zhiping Z Wang Kaitao K Bai Renren R Kang Yanhua Y Ye Xiang-Yang XY Xie Tian T

Frontiers in cell and developmental biology 20211213

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 ...[more]

PMID: 34966742

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Project description:BackgroundVentilator-induced lung injury (VILI) is caused by stretch stimulation and other factors related to mechanical ventilation (MV). NOD-like receptor protein 3 (NLRP3), an important innate immune component, is strongly associated with VILI. This study aimed to investigate the effect and mechanisms of aerobic exercise (EX) on VILI.MethodsTo test the effects of the PKC inhibitor bisindolylmaleimide I on PKC and NLRP3, male C57BL/6 mice (7 weeks old, 19 ~ 23 g) were randomly divided into four groups: control group(C), bisindolylmaleimide I-pretreated group(B), MV group, and bisindolylmaleimide I-pretreated + MV (B + MV) group. The mice were pretreated with bisindolylmaleimide I through intraperitoneal injection (0.02 mg/kg) 1 h before MV. MV was performed at a high tidal volume (30 ml/kg). To explore the ameliorative effect of EX on VILI, the mice were randomly divided into C group, MV group, EX group and EX + MV group and subjected to either MV or 5 weeks of EX training. After ventilation, haematoxylin-eosin (HE) staining and wet/dry weight ratio was used to assess lung pathophysiological changes. PKCɑ, P-PKCɑ, ASC, procaspase-1, caspase-1, pro-IL-1β, IL-1β, NLRP3 and occludin (tight junction protein) expression in lung tissues was determined by Western blotting. The level of IL-6 in alveolar lavage fluid was determined by ELISA.ResultsNLRP3, P-PKCɑ, and PKCɑ levels were inceased in MV group, but bisindolylmaleimide I treatment reversed these changes. Inhibition of PKC production prevented NLRP3 activation. Moreover, MV increased ASC, procaspase-1, caspase-1, pro-IL-1β, and IL1β levels and decreased occludin levels, but EX alleviated these changes. HE staining and lung injury scoring confirmed an absence of obvious lung injury in C group and EX group. Lung injury was most severe in MV group but was improved in EX + MV group. Overall, these findings suggest that MV activates the NLRP3 inflammasome by activating PKCɑ and inducing occludin degradation, while Exercise attenuates NLRP3 inflammasome and PKCɑ activation. Besides, exercise improves cyclic stretch-induced degradation of occludin.ConclusionPKC activation can increase the level of NLRP3, which can lead to lung injury. Exercise can reduce lung injury by inhibiting PKCɑ and NLRP3 activation. Exercise maybe a potential measure for clinical prevention of VILI.

Dataset Information

5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

Publications

5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

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