Lung injury caused by exposure to the gaseous fraction of exhaust from biomass combustion (cashew nut shells): a mice model

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

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Acetate Downregulates the Activation of NLRP3 Inflammasomes and Attenuates Lung Injury in Neonatal Mice With Bronchopulmonary Dysplasia

Frontiers in Pediatrics ◽

10.3389/fped.2020.595157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qian Zhang ◽

Xiao Ran ◽

Yu He ◽

Qing Ai ◽

Yuan Shi

Keyword(s):

Lung Injury ◽

Bronchopulmonary Dysplasia ◽

High Throughput Sequencing ◽

Intestinal Flora ◽

Inflammatory Factors ◽

Mice Model ◽

Inflammatory Reactions ◽

Caspase 1 ◽

Nlrp3 Inflammasomes

Background: Bronchopulmonary dysplasia (BPD) is a common pulmonary complication in preterm infants. Acetate is a metabolite produced by the gut microbiota, and its anti-inflammatory function is well known. The role of acetate in BPD has not been studied. Here, we investigate the effects of acetate on lung inflammation and damage in mice model of BPD.Objective: To investigate the role of acetate in the development of BPD.Methods: C57BL/6 mice were randomly divided into three groups on the 3rd day after birth: room air group, hyperoxia group, and hyperoxia + acetate (250 mM, 0.02 ml/g) group. The expression of inflammatory factors was determined by ELISA and RT-PCR, and NLRP3 and caspase-1 were detected by Western blot. High-throughput sequencing was used to detect bacterial communities in the mice intestines.Results: After acetate treatment, the expression levels of TNF-α, IL-1β, IL-18, NLRP3, and caspase-1 were significantly reduced, while the expression of GPR43 was increased. In the BPD mice treated with acetate, the proportion of Escherichia-Shigella was lower than in placebo-treated BPD mice, while the abundance of Ruminococcus was increased.Conclusions: These results indicate that acetate may regulate intestinal flora and reduce inflammatory reactions and lung injury in BPD. Therefore, acetate may be an effective drug to protect against neonatal BPD.

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MiR-574-5p alleviates sepsis-induced acute lung injury by regulating TRAF6/NF-κB pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i4.1 ◽

2020 ◽

Vol 19 (4) ◽

pp. 676-682

Author(s):

Changfu Xu ◽

Lei Chong ◽

Gang Yu ◽

Hailin Zhang

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Cell ◽

Inflammatory Responses ◽

Cecal Ligation ◽

Cytokine Expression ◽

Inflammatory Cell Infiltration ◽

Luciferase Assay ◽

Cell Infiltration ◽

Mice Model

Purpose: To investigate the protective effect of miR-574-5p pretreatment against acute lung injury (ALI) induced by sepsis.Methods: A male C57BL/6 mouse model of sepsis-induced ALI was established by cecal ligation and puncture (CLP) and treated with miR-574-5p agomir (intravenous injection, 80 mg/kg per day, 3 days). After that, blood and lung samples were obtained for histopathological observation. Myeloperoxidase (MPO) activity, inflammatory cell infiltration, and cytokine expression were analyzed. The target gene of miR-574-5p was predicted using TargetScan prediction, and verified by luciferase assay and western blot.Results: In sepsis-induced ALI mice model, downregulation of miR-574-5p was observed. Pretreatment of miR-574-5p significantly alleviated ALI by suppressing histological damage, and reducing MPO activity and inflammatory cell infiltration, as well as decreasing cytokine expression. The underlying mechanism was that miR-574-5p targeted TNF receptor associated factor 6 (TRAF6) and suppressed the downstream NF-κB pathway. Moreover, TRAF6 overexpression reversed the effects of miR-574-5p on ALI.Conclusion: MiR-574-5p pretreatment suppresses inflammatory responses, thus reducing lung injury induced by sepsis in mice, partly via the regulation of TRAF6 and NF-κB pathway. Therefore, this approach can potentially be used for the clinical management of ALI in humans Keywords: Sepsis, Acute lung injury, MiR-574-5p, TRAF6, NF-κB pathway

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Interferon Regulatory Factor 5 siRNA-Loaded Folate-Modified Cationic Liposomes for Acute Lung Injury Therapy

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3046 ◽

2021 ◽

Vol 17 (3) ◽

pp. 466-476

Author(s):

Qin Xu ◽

Mengran Guo ◽

Xiaodong Jin ◽

Quansheng Jin ◽

Zhongshan He ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Treatment Strategies ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Mice Model ◽

Interferon Regulatory Factor 5 ◽

Inflammatory State ◽

Anti Inflammatory

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an overwhelming pulmonary inflammation with limited clinical treatment strategies. Interferon regulatory factor 5 (IRF5) is a crucial regulator of inflammation factors, which can be upregulated under an inflammatory state and related to the efferocytosis of macrophages. Herein, IRF5 was knockdown by small interfering RNA (siIRF5) to promote the anti-inflammatory effect of macrophages. Macrophage-targeting cationic liposome modified by folate (FA-LP) was developed to deliver siIRF5 (FA-LP/siIRF5). Liposomes were characterized for their particle size, zeta potential, protein adsorption and hemolysis of red blood cells. The amount of IRF5 mRNA and the expression of IRF5 were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot, respectively. The phenotype and efferocytosis of macrophages and the regulatory pathway of efferocytosis and biodistribution of liposomes in the ALI mice model were investigated. Data revealed that FA-LP/siIRF5 could obviously downregulate the expression of IRF5 in macrophages, skewing the polarization of macrophages to M2 phenotype (anti-inflammatory state) and thus improving their efferocytosis. Moreover, regulation of efferocytosis of macrophages by siIRF5 is related to the NF- B pathway. The in vivo biodistribution of FA-LP exhibited higher accumulation in the inflammatory lungs, suggesting that FA-LP could be considered as a promising gene delivery system and FA-LP/siIRF5 is an alternative strategy for the treatment of ALI/ARDS. To the best of our knowledge, this is the first study reporting that siIRF5 can be used for the treatment of ALI/ARDS.

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06/00970 Health effects engineering of coal and biomass combustion particulates: influence of zinc, sulfur and process changes on potential lung injury from inhaled ash

Fuel and Energy Abstracts ◽

10.1016/s0140-6701(06)80972-0 ◽

2006 ◽

Vol 47 (2) ◽

pp. 140

Keyword(s):

Lung Injury ◽

Health Effects ◽

Biomass Combustion

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