Effects of combination of melatonin and dexamethasone on acute lung injury in a mice model of carrageenan-induced pleurisy

2006 ◽  
Vol 41 (3) ◽  
pp. 228-237 ◽  
Author(s):  
Concetta Crisafulli ◽  
Emanuela Mazzon ◽  
Carmelo Muia ◽  
PaoloDi Bella ◽  
Emanuela Esposito ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mice Model

Preventive and Therapeutic Effects of Thymol in a Lipopolysaccharide-Induced Acute Lung Injury Mice Model

Inflammation ◽  
2017 ◽  
Vol 41 (1) ◽  
pp. 183-192 ◽  
Author(s):  
Limei Wan ◽  
Dongmei Meng ◽  
Hong Wang ◽  
Shanhe Wan ◽  
Shunjun Jiang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Effects ◽  
Mice Model

scholarly journals Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction

2017 ◽  
Author(s):  
Jingjing Wang ◽  
Jian Xu ◽  
Xinyun Zhao ◽  
Weiping Xie ◽  
Hong Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Rho Kinase ◽  
Intercellular Junctions ◽  
Intercellular Adhesion Molecule ◽  
Mice Model ◽  
Rock Inhibitor ◽  
Histological Changes ◽  
Endothelial Apoptosis ◽  
Cytokine Levels

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.

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

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

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

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.

Icariside II regulates TLR4/NF-κB signaling pathway to improve septic lung injury

2021 ◽  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Mortality ◽  
Biological Activities ◽  
Flavonoid Compound ◽  
Therapeutic Drug ◽  
Inadequate Response ◽  
Mice Model ◽  
Stress Injury ◽  
Icariside Ii

Sepsis is caused by the inadequate response to infection and may eventually lead to fatal organ dysfunction and a high mortality rate. Acute lung injury (ALI) caused by sepsis is an important cause of its high mortality, so effective treatment drugs are urgently needed. Icariside II (ICA II) is derived from Epimedii, a ubiquitous biological flavonoid compound. ICA II has shown multiple biological activities. ICA II alleviates LPS-induced neuroinflammation by inhibiting the TLR4 / MyD88 /NF-κB pathway, however, the possible role of icaridinin II in sepsis induced acute lung injury remains unclear. Herein, we developed a sepsis-related ALI mice model induced by LPS treatment, and found Icariside II ameliorated sepsis-related acute lung injury of mice induced by LPS. Our data further confirmed that Icariside II inhibited the inflammatory response in sepsis-related ALI mice, and ameliorated oxidative stress injury. We further revealed Icariside II inhibited the apoptosis of lung cells via TLR4-NF-κB axis. Our data therefore provided a promising therapeutic drug for the treatment of sepsis-induced ALI.

Seabuckthorn Berries Attenuate Pulmonary Vascular Hyperpermeability in Lipopolysaccharide-induced Acute Lung Injury in Mice

2020 ◽  
Author(s):  
Leilei Du ◽  
Ying Liu ◽  
Li Wan ◽  
Chu Chen ◽  
Gang Fan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mice Model ◽  
Key Factors ◽  
Capillary Barrier ◽  
Endotoxin Challenge ◽  
Tnf Α ◽  
Short Term Mortality ◽  
Sparse Methods ◽  
Alveolar Capillary

Abstract Background Acute lung injury is featured by pulmonary vascular hyperpermeability, resulting in high short-term mortality. Currently pharmacological therapies are still sparse. Methods In the mice model of acute lung injury induced by Lipopolysaccharide, the effect of seabuckthorn berries extract on pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. The key factors involved in alveolar-capillary barrier lesion were assessed. Results The findings indicated that treatment of seabuckthorn berries alleviated morphological lesion as well as water, Evans blue and total proteins leakage in lung tissue, suppressed the release of TNF-α and IL-6, decreased accumulation of neutrophils, inhibited the activation of NF-κB and down-regulated the expression of ICAM-1 and CD62E. Conclusions These results demonstrated seabuckthorn berries help maintaining alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of acute lung injury.

scholarly journals Role of cholinergic anti-inflammatory pathway in protecting sepsis-induced acute lung injury through regulation of the dendritic cells

2021 ◽  
Author(s):  
Ruiting Li ◽  
Xuemei Hu ◽  
Huibin Chen ◽  
Yin Yuan ◽  
Huiling Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Mice Model ◽  
Pro Inflammatory Cytokines

Abstract Background The cholinergic anti-inflammatory pathway (CAP) connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR), which is localized on the surface of the cells of immune system. CAP has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells (APCs), also express the α7nAChR. They not only play an important role in immune response priming but also in participating in the pathological process of ALI. Past studies have indicated that reducing the quantity of mature conventional DCs (cDCs) and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of CAP on maturation, function and quantity of DCs and cDCs in ALI remain unclear. Objective It was hypothesized that the activation of CAP may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and cDCs. This can be considered as an important intervention strategy for treating ALI. Methods GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist was administered in sepsis-induced ALI mice model and LPS-primed bone marrow-derived dendritic cells (BMDCs). The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, cDCs, and cDCs2 (type 2 cDCs), and the release of DC-related pro-inflammatory cytokines (such as IL-6, TNF-α, IL-18 IL-1β, IL-12p40, and HMGB1) in vivo and in vitro conditions. Results The results of the present study revealed that, GTS-21 treatment regulated the maturation of DCs and the production of DC-related pro-inflammatory cytokines in vitro and in sepsis-induced ALI mice model, it reduced the quantity of CD11c+MHCII+ cDCs and CD11c+CD11b+ cDCs2 in vivo experiment. Conclusions The activation of CAP contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, cDCs, and cDCs2.

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