High-Fat Diet Increases HMGB1 Expression and Promotes Lung Inflammation in Mice Subjected to Mechanical Ventilation

Souza, Ana Beatriz Farias de; Chírico, Máira Tereza Talma; Cartelle, Christiane Teixeira; Costa, Guilherme de Paula; Talvani, André; Cangussú, Sílvia Dantas; Menezes, Rodrigo Cunha Alvim de; Bezerra, Frank Silva

doi:10.1155/2018/7457054

Cited by 22 publications

(18 citation statements)

References 64 publications

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“…We found that CS at 20% tension triggered PINK1/PRKN-mediated mitophagy. Mechanical ventilation has been demonstrated to induce the oxidative damage of mitochondria, up-regulating the high-mobility group box1 and nuclear factor-erythroid 2-related factor 2 ( Dong et al, 2015 ; de Souza et al, 2018 ). Such mitophagy is activated to eliminate damaged mitochondria, leading to the accumulation of reactive oxygen species and a decrease in ΔψM ( Hou et al, 2018 ; Lin et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway

Ren

Lin

et al. 2020

Front. Cell Dev. Biol.

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Background: In animal models of ventilation-induced lung injury, mitophagy triggers mitochondria damage and the release of mitochondrial (mt) DNA, which activates inflammation. However, the mechanism of this process is unclear. Methods: A model of cyclic stretching (CS)-induced lung epithelial cell injury was established. The genetic intervention of phosphatase and tensin homolog-induced kinase 1 (PINK1) expression via lentivirus transfection was used to identify the relationship between PINK1-mediated mitophagy and mtDNA release in stretchinginduced inflammatory response and injury. Pharmacological inhabitation of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) expression was performed via their related inhibitors, while pre-treatment of exogenous mtDNA was used to verify the role of mtDNA in stretching-induced inflammatory response and injury. Results: Using a cell culture model of CS, we found that knocking down PINK1 in lung epithelial cells reduced mitophagy activation and mtDNA release, leading to milder inflammatory response and injury; conversely, up-regulating PINK1 exacerbated stretching-induced inflammation and injury, and similar effects were observed by upregulating TLR9 to induce expression of MyD88 and nuclear factor-κB (NF-κB)/p65. Down-regulating MyD88 protected lung epithelial cells from stretching injury and decreased NF-κB/p65 expression. Conclusion: These findings suggest that PINK1-dependent mitophagy and associated TLR9 activation is indeed a major factor in stretch-induced cell injury via a mechanism

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Section: Discussionmentioning

confidence: 99%

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway

Ren

Lin

et al. 2020

Front. Cell Dev. Biol.

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“…Morphometric analysis of the sections stained by immunohistochemistry was performed in 20 random fields of the slides photographed at a magnification of × 20 using ImageJ 1.6.0 software. In each field, the total number of nuclei and the number of nuclei labeled for the antibody used were counted, and the ratio of labeled nuclei/total nuclei was calculated [30].…”

Section: Methodsmentioning

confidence: 99%

Exogenous surfactant prevents hyperoxia-induced lung injury in adult mice

Bezerra

Ramos

Castro

et al. 2019

ICMx

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Background In addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia. Methods Male BALB/c mice (8–10 weeks), a strain highly sensitive to hyperoxia, received the exogenous surfactant-containing protein SP-B and SP-C by intranasal instillation 12 h before starting 24 h of exposure to hyperoxia in an inhalation chamber and were compared to mice receiving hyperoxia alone and to controls subjected to normoxia. Results Compared to the hyperoxia group, the administration of exogenous surfactant was able to reduce lung inflammation through a reduction in the influx of neutrophils and inflammatory biomarkers such as TNF, IL-17, and HMGB1 expression. The antioxidant activity prevented oxidative damage by reducing lipid peroxidation and protein carbonylation and increasing superoxide dismutase activity when compared to the hyperoxia group. Conclusion Our results offer new perspectives on the effects and the mechanism of exogenous surfactant in protecting the airway and lungs, in oxygen-rich lung microenvironment, against oxidative damage and aggravation of acute inflammation induced by hyperoxia.

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“…However, IL-17 levels in BAL fluid showed an opposite trend, where IL-17 levels were higher in VAP than non-VAP patients, though it should be noted that IL-17 levels in most of the patients were below the limit of detection of the assay [16]. Similarly, although IL-17 in VAP animal models has not been studied, mice ventilated for one hour with V T 7 mL/kg were reported to have increased IL-22 but decreased IL-17 levels [17].…”

Section: Introductionmentioning

confidence: 99%

Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia

Winter

Jongers

Bielen

et al. 2019

IJMS

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Mechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked by increased IL-4 secretion and reduced bacterial phagocytic capacity of rodent lung macrophages. Since IL-4 is known to downregulate both Th1 and Th17 cytokines, the latter is important in mediating mucosal immunity and combating bacterial and fungal growth, we studied and showed here in a rat model of MV that Th17 cytokines (IL-17A, IL-17F, and IL-22) were significantly upregulated in the lung as a response to different MV strategies currently utilized in clinic. To study whether the increased IL-4 levels are associated with downregulation of the anti-bacterial Th17 cytokines, we subsequently challenged mechanically ventilated rats with an intratracheal inoculation of Pseudomonas aeruginosa (VAP model) and showed a dramatic downregulation of IL-17A, IL-17F, and IL-22, compared to animals receiving the same bacterial burden without MV. For the studied Th1 cytokines (IFNγ, TNFα, IL-6, and IL-1β), only IFNγ showed a significant decrease as a consequence of bacterial infection in mechanically ventilated rats. We further studied IL-17A, the most studied IL-17 family member, in intensive care unit (ICU) pneumonia patients and showed that VAP patients had significantly lower levels of IL-17A in the endotracheal aspirate compared to patients entering ICU with pre-existing pneumonia. These translational data, obtained both in animal models and in humans, suggest that a deficient anti-bacterial Th17 response in the lung during MV is associated with VAP development.

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High-Fat Diet Increases HMGB1 Expression and Promotes Lung Inflammation in Mice Subjected to Mechanical Ventilation

Cited by 22 publications

References 64 publications

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway

Exogenous surfactant prevents hyperoxia-induced lung injury in adult mice

Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia

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