scholarly journals Apelin-13 Administration Protects Against LPS-Induced Acute Lung Injury by Inhibiting NF-κB Pathway and NLRP3 Inflammasome Activation

2018 ◽  
Vol 49 (5) ◽  
pp. 1918-1932 ◽  
Author(s):  
Hailin Zhang ◽  
Sha Chen ◽  
Meichun Zeng ◽  
Daopeng Lin ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Structural Damage ◽  
Cell Model ◽  
Weight Ratio ◽  
Inflammatory Factors ◽  
Mouse Lung ◽  
Inflammasome Activation ◽  
Ros Formation

Background/Aims: Acute lung injury (ALI) is induced by a variety of external and internal factors and leads to acute progressive respiratory failure. Previous studies have shown that apelin-13 can decrease the acute lung injury induced by LPS, but the specific mechanism is unclear. Therefore, a mouse lung injury model and a cell model were designed to explore the mechanism of how apelin-13 alleviates the acute lung injury caused by LPS. Methods: The effect of apelin-13 on LPS-induced structural damage was determined by H&E staining and by the wet/dry weight ratio. The related inflammatory factors in BALF were examined by ELISA. The apoptotic pathway and the NF-κB and NLRP3 inflammasome pathways were evaluated by using Western blotting and immunofluorescence staining. Results: LPS induced the structural damage and the production of inflammatory cytokines in the lung tissues of mice. These deleterious effects were attenuated by apelin-13 administration. The protective effects of apelin-13 were associated with decreased reactive oxygen species (ROS) formation and the inhibition of the activation of the NF-κB and NLRP3 inflammasome pathways in mice and in Raw264.7 cells. Conclusion: Taken together, these data suggest that apelin-13 administration ameliorates LPS-induced acute lung injury by suppressing ROS formation, as well as by inhibiting the NF-κB pathway and the activation of the NLRP3 inflammasome in the lungs.

scholarly journals Tanshinone IIA ameliorates acute lung injury by inhibition of the NLRP3 inflammasome

2019 ◽  
Vol 71 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Tianyu Chen ◽  
Shaoyun Qin ◽  
Ying Dai
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Partial Pressure ◽  
Nlrp3 Inflammasome ◽  
Weight Ratio ◽  
Dry Weight ◽  
Tanshinone Iia ◽  
Inflammasome Activation ◽  
Co2 Partial Pressure ◽  
O2 Partial Pressure

Tanshinone IIA is the phenanthrenequinone derivative extracted from the perennial plant Salvia miltiorrhiza Bunge (red sage). We investigated whether inhibition of the nucleotide-binding oligomerization domain (NOD)-like receptor family protein 3 (NLRP3) inflammasome mediates the protective effect of tanshinone IIA in acute lung injury (ALI) induced in rats by oleic acid (OA) injection. Compared with the control treatment, OA injection induced pulmonary histological impairment, increased the lung wet/dry weight ratio (7.0?1.1 vs 4.?0.6 ) and CO2 partial pressure (PaCO2) (52?6.4 vs 40?3.6 mmHg), decreased arterial O2 partial pressure (PaO2) (63?8.4 vs 100?3.0 mmHg), and increased tumor necrosis factor ? (TNF?) (8.8?2.3 vs 5.2 ?1.5 pg/mL), monocyte chemoattractant protein-1 (MCP-1) (36.1?4.9 vs 25.2?6.6 pg/mL) and interleukin-1? (IL-1?) (15.9?3.2 vs 4.6?1.3 pg/mL) in the bronchoalveolar lavage (BAL) fluid. Tanshinone IIA provided protection against ALI, observed as a reduction in the lung wet/dry weight ratio and CO2 partial pressure, and increased O2 partial pressure. The cytokine increase was also prevented. Tanshinone IIA attenuated increased protein levels of NLRP3, caspase-1 and IL-1? in pulmonary tissues, suggesting that it ameliorates ALI by preventing NLRP3 inflammasome activation.

scholarly journals Extracellular mitochondrial DNA promote NLRP3 inflammasome activation and induce acute lung injury through TLR9 and NF-κB

2019 ◽  
Vol 11 (11) ◽  
pp. 4816-4828 ◽  
Author(s):  
Guannan Wu ◽  
Qingqing Zhu ◽  
Junli Zeng ◽  
Xiaoling Gu ◽  
Yingying Miao ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Anemoside B4 Protects against Acute Lung Injury by Attenuating Inflammation through Blocking NLRP3 Inflammasome Activation and TLR4 Dimerization

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Renyikun Yuan ◽  
Jia He ◽  
Liting Huang ◽  
Li-Jun Du ◽  
Hongwei Gao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Macrophage Cells ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

Acute lung injury (ALI) is an acute inflammatory process in the lung parenchyma. Anemoside B4 (B4) was isolated from Pulsatilla, a plant-based drug against inflammation and commonly applied in traditional Chinese medicine. However, the anti-inflammatory effect and the mechanisms of B4 are not clear. In this study, we explored the potential mechanisms and anti-inflammatory activity of B4 both in vitro and in vivo. The results indicated that B4 suppressed the expression of iNOS, COX-2, NLRP3, caspase-1, and IL-1β. The ELISA assay results showed that B4 significantly restrained the release of inflammatory cytokines like TNF-α, IL-6, and IL-1β in macrophage cells. In addition, B4 rescued mitochondrial membrane potential (MMP) loss in (lipopolysaccharide) LPS plus ATP stimulated macrophage cells. Co-IP and molecular docking results illustrated that B4 disrupted the dimerization of TLR4. For in vivo results, B4 exhibited a protective effect on LPS and bleomycin- (BLM-) induced ALI in mice through suppressing the lesions of lung tissues, the release of inflammatory cytokines, and the levels of white blood cells, neutrophils, and lymphoid cells in the blood. Collectively, B4 has a protective effect on ALI via blocking TLR4 dimerization and NLRP3 inflammasome activation, suggesting that B4 is a potential agent for the treatment of ALI.

scholarly journals Mechanism of MCP-1 in Acute Lung Injury and Advanced Therapy by Drug-Loaded Dextrin Nanoparticle

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Zheng Cao ◽  
Jing-Lan Liu ◽  
Shen Wu ◽  
Qiao Wang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Blood Gas Analysis ◽  
Gas Analysis ◽  
Inflammatory Factors ◽  
Saline Control ◽  
Mrna Levels ◽  
Blood Gas ◽  
Wet Weight

Objective. To observe the expression of monocyte chemotactic protein 1 (MCP-1) in acute lung injury (ALI) rat model, to characterize its effect on the development and progression of ALI, and to identify the potential new drug delivery approach during in vivo experiment. Method. The effects of different doses of lipopolysaccharide (LPS) on human pulmonary artery endothelial cells (HPAEC) were tested. For the animal experiments, thirty Sprague-Dawley (SD) rats were divided into physiological saline control group (NC group), the LPS model group (L group), the antagonist RS102895 combined with LPS group (R + L group), and the antagonist RS102895-loaded polyaldehyde dextran nanoparticles combined with LPS group (DNPR + L group). The blood gas analysis and dry/wet weight ratio were detected 24 hours after interventions. The levels of inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were tested by ELISA. The expression of monocyte chemoattractant protein-1 (MCP-1) in lung tissues was examined through Western blot, and the change of MCP-1 mRNA expression level was detected by performing RT-PCR. Result. LPS was responsible for inducing ALI in rats, and the degree of cell damage was dose-dependent. Blood gas analysis of L group showed that PaO2 and PaO2/FiO2 levels were significantly lower than those of the NC group (P<0.05), while the dry/wet weight ratio of lung tissues in L group increased (P<0.05). Inflammatory factors including TNF-α and IL-1β and the expression of MCP-1 in both protein and mRNA levels were higher in L group than in the NC group (P<0.05). The inhibition of the interaction between MCP-1 and chemokines receptor 2 (CCR2) by antagonist RS102895 can significantly alleviate the ALI in rats, which is accompanied by a significant decrease of inflammatory factors and MCP-1 expression (P<0.05). Compared with R + L group, treatment with DNPR and LPS combination significantly improved the condition of rats and decreased the level of TNF-α, IL-1β, and MCP-1 expression (P<0.05). Conclusion. In ALI, RS102895 can inhibit the MCP-1/CCR2 interaction, therefore, retarding the progress of ALI. Because of the high transfection efficiency of inhibitor RS102895packgaed by polyaldehyde dextran nanoparticles, this phenomenon particularly reached a significant level. The results imply new insights for the treatment of ALI.

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