Mitochondria and their potential role in acute lung injury (Review)

Zhan, Biao; Shen, Jie

doi:10.3892/etm.2022.11406

Cited by 9 publications

(1 citation statement)

References 219 publications

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“…Mitochondrial dysfunction, characterized by decreased ATP production, membrane potential and expression of mitochondrial complexes I, III, IV, but increased reactive oxygen species (ROS) [ 1 ], has been observed in inflamed lungs of various diseases such as asthma [ 2 , 3 , 4 ], chronic pulmonary obstructive disease (COPD), pulmonary fibrosis [ 5 ] and acute lung injury [ 6 ]. One of the biomarkers for mitochondrial dysfunction during the inflammatory process is increased release of mitochondrial DNA (mtDNA).…”

Section: Introductionmentioning

confidence: 99%

Role of Myeloid Cell-Specific TLR9 in Mitochondrial DNA-Induced Lung Inflammation in Mice

Dimasuay

Berg

Schaunaman

et al. 2023

IJMS

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Mitochondrial dysfunction is common in various pathological conditions including obesity. Release of mitochondrial DNA (mtDNA) during mitochondrial dysfunction has been shown to play a role in driving the pro-inflammatory response in leukocytes including macrophages. However, the mechanisms by which mtDNA induces leukocyte inflammatory responses in vivo are still unclear. Moreover, how mtDNA is released in an obese setting has not been well understood. By using a mouse model of TLR9 deficiency in myeloid cells (e.g., macrophages), we found that TLR9 signaling in myeloid cells was critical to mtDNA-mediated pro-inflammatory responses such as neutrophil influx and chemokine production. mtDNA release by lung macrophages was enhanced by exposure to palmitic acid (PA), a major saturated fatty acid related to obesity. Moreover, TLR9 contributed to PA-mediated mtDNA release and inflammatory responses. Pathway analysis of RNA-sequencing data in TLR9-sufficient lung macrophages revealed the up-regulation of axon guidance molecule genes and down-regulation of metabolic pathway genes by PA. However, in TLR9-deficient lung macrophages, PA down-regulated axon guidance molecule genes, but up-regulated metabolic pathway genes. Our results suggest that mtDNA utilizes TLR9 signaling in leukocytes to promote lung inflammatory responses in hosts with increased PA. Moreover, TLR9 signaling is involved in the regulation of axon guidance and metabolic pathways in lung macrophages exposed to PA.

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Section: Introductionmentioning

confidence: 99%

Role of Myeloid Cell-Specific TLR9 in Mitochondrial DNA-Induced Lung Inflammation in Mice

Dimasuay

Berg

Schaunaman

et al. 2023

IJMS

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The multifaceted role of macrophage mitophagy in SiO₂‐induced pulmonary fibrosis: A brief review

Zhou,

Li,

et al. 2024

J of Applied Toxicology

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Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2‐induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2‐induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2‐induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy‐inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2‐induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

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Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice

Zhang,

Zhao,

Wang

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Acute lung injury (ALI) is a common disease with complex pathogenesis. However, the treatment is mainly symptomatic with limited clinical options. Asiaticoside (AS), a Chinese herbal extract, has protective effects against LPS-induced ALI in mice and inhibits nitric oxide and prostaglandin E2 synthesis; however, the specific mechanism of AS in the prevention and treatment of LPS-induced ALI needs further study. Sema4D/CD72 pathway, mitochondrial dysfunction, and miRNA-21 are closely associated with inflammation. Therefore, the present study aimed to explore whether AS exerts its therapeutic effect on ALI by influencing Sema4D/CD72 pathway and mitochondrial dysfunction, restoring the balance of inflammatory factors, and influencing miRNA-21 expression. Cell and animal experiments were performed to investigate the effect of AS on ALI. Lipopolysaccharide (LPS) was used to establish the ALI model. CCK8 and flow cytometry were used to detect the cell viability and apoptosis rate. HE staining and wet-to-dry weight ratio (W/D) of lung tissue were determined. The expressions of Sema4D, CD72, NF-κB p65, Bax, Bcl2, and caspase 3 in RAW264.7 cells and lung tissues were detected by western blot, and the levels of IL-10 and IL-1β induced by LPS in supernatant of RAW264.7 cells and BALF were measured by ELISA. And the expression of miRNA-21 in cells and lung tissues was detected by fluorescence quantitative PCR. The result shows that AS treatment suppressed LPS-induced cell damage and lung injury in mice. AS treatment could alleviate the pathological changes such as inflammatory infiltration and histopathological changes in the lungs caused by LPS, and reduce the ratio of W/D. AS significantly alleviated the decrease of mitochondrial membrane potential induced by LPS, inhibited the increase of ROS production, and reduced the expression of mitochondrial fission proteins Drp1 and Fis1. The high-dose AS group significantly downregulated the expression of Sema4D, CD72, phosphorylated NF-κB p65, and apoptosis-related proteins, decreased the pro-inflammatory factor IL-1β, and enhanced the level of anti-inflammatory factor IL-10. In addition, AS promoted miRNA-21 expression. These effects inhibited apoptosis and restored the balance between anti- and pro-inflammatory factors. This represents the inaugural report elucidating the mechanism by which AS inhibits the Sema4D/CD72 signaling pathway. These findings offer novel insights into the potential application of AS in both preventing and treating ALI.

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Mitochondria and their potential role in acute lung injury (Review)

Cited by 9 publications

References 219 publications

Role of Myeloid Cell-Specific TLR9 in Mitochondrial DNA-Induced Lung Inflammation in Mice

Role of Myeloid Cell-Specific TLR9 in Mitochondrial DNA-Induced Lung Inflammation in Mice

The multifaceted role of macrophage mitophagy in SiO₂‐induced pulmonary fibrosis: A brief review

Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice

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Mitochondria and their potential role in acute lung injury (Review)

Cited by 9 publications

References 219 publications

Role of Myeloid Cell-Specific TLR9 in Mitochondrial DNA-Induced Lung Inflammation in Mice

Role of Myeloid Cell-Specific TLR9 in Mitochondrial DNA-Induced Lung Inflammation in Mice

The multifaceted role of macrophage mitophagy in SiO2‐induced pulmonary fibrosis: A brief review

Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice

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The multifaceted role of macrophage mitophagy in SiO₂‐induced pulmonary fibrosis: A brief review