scholarly journals Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM 2 .5 in mice

2021 ◽  
Author(s):  
Mengmeng Xu ◽  
Xiaohui Wang ◽  
Lu Xu ◽  
Hai Zhang ◽  
Chenfei Li ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Inflammation ◽  
Intranasal Instillation

scholarly journals Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM2.5 in mice

2020 ◽  
Author(s):  
Mengmeng Xu ◽  
Hai Zhang ◽  
Lu Xu ◽  
Xiaohui Wang ◽  
Chenfei Li ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Inflammation ◽  
Type I Collagen ◽  
Epithelial Mesenchymal Transition ◽  
Fine Particulate Matter ◽  
Type I ◽  
Mesenchymal Transition ◽  
Pm 2.5 ◽  
Cell Counts ◽  
Intranasal Instillation

Abstract Background: Fine particulate matter (PM 2.5 ) is an important component of air pollution and can induce lung inflammation and oxidative stress. We hypothesised that PM 2.5 could play a role in the induction of pulmonary fibrosis. We examined whether multiple intranasal instillation of PM 2.5 can induce pulmonary fibrosis in the mouse, and also investigated the underlying pro-fibrotic signaling pathways.Methods: C57/BL6 mice were intranasally instilled with 50 μl of PM 2.5 suspension (7.8 μg/g body weight) or PBS three times a week over 3 weeks, 6 weeks or 9 weeks. To observe the recovery of pulmonary fibrosis after the termination of PM 2.5 exposure, 9 week-PM 2.5 instilled mice were also studied at 3 weeks after termination of instillation.Results: There were significant decreases in total lung capacity (TLC) and compliance (Cchord) in the 9-week PM 2.5 -instilled mice, while there was an increase in total cell counts in bronchoalveolar fluid and lung section in 3-week, 6-week and 9-week PM 2.5 -instilled mice and 9 week-PM 2.5 instilled-3 week-air exposed mice. There were increased histological fibrosis scores with enhanced type I collagen and hydroxyproline deposition in lung tissue in 6-week and 9-week PM 2.5 -instilled mice and 9-week-PM 2.5 instilled-3-week-air-exposed mice. Multiple PM 2.5 instillation resulted in increased expression of TGFβ1, increases of N-Cadherin and Vimentin and decrease of E-Cadherin. It also led to decreases in OPA1 and MFN2, and increases in Parkin, SQSTM1/p62, the ratio of light china (LC) 3B II to LC3B I, PI3k/Akt phosphorylation, NOX4 and NLRP3 expression.Conclusions: The intranasal instillation of PM 2.5 for 9 weeks induced lung inflammation and pulmonary fibrosis, which was linked with aberrant epithelial-mesenchymal transition, mitochondrial damage and mitophagy, as well as activation of TGFβ1-PI3K/Akt and TGFβ1-NOX4 -NLRP3 pathways.

scholarly journals Selective Myeloid Depletion of Galectin-3 Offers Protection Against Acute and Chronic Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Duncan C. Humphries ◽  
Ross Mills ◽  
Ross Dobie ◽  
Neil C. Henderson ◽  
Tariq Sethi ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Respir Crit ◽  
Pulmonary Inflammation ◽  
Myeloid Cell ◽  
Clinical Development ◽  
Galectin 3 ◽  
Direct Targeting

Rationale: Galectin-3 (Gal-3) is an immune regulator and an important driver of fibrosis in chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Previous work has shown that global deletion of galectin-3 reduces collagen deposition in a bleomycin-induced pulmonary fibrosis model (MacKinnon et al., Am. J. Respir. Crit. Care Med., 2012, 185, 537–46). An inhaled Gal-3 inhibitor, GB0139, is undergoing Phase II clinical development for idiopathic pulmonary fibrosis (IPF). This work aims to elucidate the role of Gal-3 in the myeloid and mesenchymal compartment on the development of acute and chronic lung injury.Methods:LgalS3fl/fl mice were generated and crossed with mice expressing the myeloid (LysM) and mesenchymal (Pdgfrb) cre drivers to yield LysM-cre+/-/LgalS3fl/fl and Pdgfrb-cre+/-/LgalS3fl/fl mice. The response to acute (bleomycin or LPS) or chronic (bleomycin) lung injury was compared to globally deficient Gal-3−/− mice.Results: Myeloid depletion of Gal-3 led to a significant reduction in Gal-3 expression in alveolar macrophages and neutrophils and a reduction in neutrophil recruitment into the interstitium but not into the alveolar space. The reduction in interstitial neutrophils corelated with decreased levels of pulmonary inflammation following acute bleomycin and LPS administration. In addition, myeloid deletion decreased Gal-3 levels in bronchoalveolar lavage (BAL) and reduced lung fibrosis induced by chronic bleomycin. In contrast, no differences in BAL Gal-3 levels or fibrosis were observed in Pdgfrb-cre+/-/LgalS3fl/flmice.Conclusions: Myeloid cell derived Galectin-3 drives acute and chronic lung inflammation and supports direct targeting of galectin-3 as an attractive new therapy for lung inflammation.

scholarly journals DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 938 ◽  
Author(s):  
Soo Jung Cho ◽  
Kyoung Sook Hong ◽  
Ji Hun Jeong ◽  
Mihye Lee ◽  
Augustine M. K. Choi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Protein Expression ◽  
Alveolar Macrophages ◽  
Lung Inflammation ◽  
Mirna Biogenesis ◽  
Inflammasome Activation ◽  
Dependent Lung ◽  
Ribonuclease Iii ◽  
Primary Mouse

Idiopathic pulmonary fibrosis (IPF) has been linked to chronic lung inflammation. Drosha ribonuclease III (DROSHA), a class 2 ribonuclease III enzyme, plays a key role in microRNA (miRNA) biogenesis. However, the mechanisms by which DROSHA affects the lung inflammation during idiopathic pulmonary fibrosis (IPF) remain unclear. Here, we demonstrate that DROSHA regulates the absent in melanoma 2 (AIM2) inflammasome activation during idiopathic pulmonary fibrosis (IPF). Both DROSHA and AIM2 protein expression were elevated in alveolar macrophages of patients with IPF. We also found that DROSHA and AIM2 protein expression were increased in alveolar macrophages of lung tissues in a mouse model of bleomycin-induced pulmonary fibrosis. DROSHA deficiency suppressed AIM2 inflammasome-dependent caspase-1 activation and interleukin (IL)-1β and IL-18 secretion in primary mouse alveolar macrophages and bone marrow-derived macrophages (BMDMs). Transduction of microRNA (miRNA) increased the formation of the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks, which is required for AIM2 inflammasome activation in BMDMs. Our results suggest that DROSHA promotes AIM2 inflammasome activation-dependent lung inflammation during IPF.

Low-level laser therapy attenuates lung inflammation and airway remodeling in a murine model of idiopathic pulmonary fibrosis: Relevance to cytokines secretion from lung structural cells

2020 ◽  
Vol 203 ◽  
pp. 111731 ◽  
Author(s):  
Auriléia Aparecida de Brito ◽  
Elaine Cristina da Silveira ◽  
Nicole Cristine Rigonato-Oliveira ◽  
Stephanie Souza Soares ◽  
Maysa Alves Rodrigues Brandao-Rangel ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Laser Therapy ◽  
Murine Model ◽  
Lung Inflammation ◽  
Airway Remodeling ◽  
Low Level Laser Therapy ◽  
Low Level Laser ◽  
Level Laser ◽  
Cytokines Secretion

scholarly journals Pleurotus eryngiiAmeliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Junya Kawai ◽  
Tsugunobu Andoh ◽  
Kenji Ouchi ◽  
Satoshi Inatomi
Keyword(s):  
Lung Inflammation ◽  
Pulmonary Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Beneficial Effects ◽  
Lps Challenge ◽  
Heat Treated ◽  
Cultivated Mushroom ◽  
Anti Inflammatory ◽  
Intranasal Instillation

Pleurotus eryngii(P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect ofP. eryngiiin mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10 μg/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treatedP. eryngii(0.3–1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus,P. eryngiiitself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

scholarly journals Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167729 ◽  
Author(s):  
Taiki Kida ◽  
Shinya Ayabe ◽  
Keisuke Omori ◽  
Tatsuro Nakamura ◽  
Toko Maehara ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Inflammation ◽  
Prostaglandin D2

Intranasal instillation of distilled water, hypertonic saline and sodium bicarbonate promotes redox imbalance and acute lung inflammation in adult mice

2019 ◽  
Vol 266 ◽  
pp. 27-32 ◽  
Author(s):  
Sophia Dias Pozzolini Fróes ◽  
Ana Beatriz Farias de Souza ◽  
Natália Alves de Matos ◽  
Nicole Elizabeth Philips ◽  
Guilherme de Paula Costa ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
Hypertonic Saline ◽  
Lung Inflammation ◽  
Distilled Water ◽  
Acute Lung Inflammation ◽  
Redox Imbalance ◽  
Adult Mice ◽  
Intranasal Instillation

Agmatine attenuates silica-induced pulmonary fibrosis

2014 ◽  
Vol 33 (6) ◽  
pp. 650-660 ◽  
Author(s):  
DS El-Agamy ◽  
MH Sharawy ◽  
EM Ammar
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Inflammation ◽  
Tissue Injury ◽  
Large Body ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
No Production ◽  
Protective Effects ◽  
Sprague Dawley

There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase ( p < 0.001) and reduced glutathione ( p < 0.05) activities with significant decrease in the lung malondialdehyde ( p < 0.001) content as compared to the silica group. Agmatine also reduced silica-induced overproduction of pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects.

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