scholarly journals Emodin alleviates LPS-induced inflammatory response in lung injury mice by affecting the function of neutrophils

2020 ◽  
Author(s):  
Hongxia Mei ◽  
Ying Tao ◽  
Tianhao Zhang ◽  
Feng Qi
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Respiratory Burst ◽  
Neutrophil Function ◽  
Dependent Manner ◽  
Lower Lung ◽  
Microscopy Analysis ◽  
The Right

Abstract Background: This study aims to investigate the role of Emodin(Emo) on the pulmonary inflammatory response and the neutrophil function in a murine model of lipopolysaccharide (LPS)-induced ALI. The mouse model of lipopolysaccharide (LPS)-induced ALI was produced by acute lung injury of injecting 20 mg/kg LPS via the caudal vein.The right lower lung lobes were harvested, fixed,embedded and stained with hematoxylin and eosin (H&E) for light microscopy analysis to evaluate lung injury. TNF-αand IL-1 ELISA kits were used to detect the levels of TNF-α and IL-1 in the right lung homogenate of rats. The primary rat neutrophils were separated and treated with LPS to mimic a ALI cellular model. The expression of Respiratory burst and Neutrophil NETs Production was examined using spectrophotometer.The Elastase release was detected using Elastase Activity Assay kit.The ROS Production was measured by Luminometer.the phagocytosis of Neutrophils and the rate of apoptotic Neutrophils were measured by flow cytometry. Results: This study demonstrates that Emo alleviates lung injury and reduces the release of inflammatory cytokines. Moreover, Emo also downregulated neutrophil respiratory burst and the production of ROS in the LPS-stimulated neutrophils, thus reducing the damage of neutrophils to the surrounding tissues. Emo can also up-regulate the ability of neutrophils to phagocytize bacteria and generate NETs, thereby enhancing the bactericidal ability of neutrophils. In addition, Emo can promote the apoptosis of neutrophils and accelerate the resolution of inflammation. Conclusion: Emo has a protection effect on LPS-induced acute lung injury mice. It can alleviate lung injury and reduces the release of inflammatory cytokines, perhaps by affecting the various function of neutrophils in a dose-dependent manner.

scholarly journals Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of neutrophils

2020 ◽  
Author(s):  
Hongxia Mei ◽  
Ying Tao ◽  
Tianhao Zhang ◽  
Feng Qi
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Rat Model ◽  
Neutrophil Function ◽  
Life Threatening ◽  
Pulmonary Inflammatory Response ◽  
Anti Inflammatory ◽  
Factor Α ◽  
The Impact

Abstract Background: Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of neutrophils that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the neutrophil function in a rat model of lipopolysaccharide (LPS)-induced ALI.Results: Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with neutrophil deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced neutrophils via the up-regulation of the ability of neutrophils to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the neutrophil respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated neutrophils, alleviating the damage of neutrophils to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of neutrophils. Conclusion: Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of neutrophils. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.

scholarly journals Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of neutrophils

2020 ◽  
Author(s):  
Hongxia Mei ◽  
Ying Tao ◽  
Tianhao Zhang ◽  
Feng Qi
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Rat Model ◽  
Neutrophil Function ◽  
Life Threatening ◽  
Pulmonary Inflammatory Response ◽  
Anti Inflammatory ◽  
Factor Α ◽  
The Impact

Abstract Background: Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of neutrophils that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the neutrophil function in a rat model of lipopolysaccharide (LPS)-induced ALI.Results: Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with neutrophil deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced neutrophils via the up-regulation of the ability of neutrophils to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the neutrophil respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated neutrophils, alleviating the damage of neutrophils to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of neutrophils. Conclusion: Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of neutrophils. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.

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.

scholarly journals Oxypaeoniflorin Prevents Acute Lung Injury Induced by Lipopolysaccharide through the PTEN/AKT Pathway in a Sirt1-Dependent Manner

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Fan Guohua ◽  
Zhu Tieyuan ◽  
Wang Rui ◽  
Xiong Juan
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Alveolar Epithelial Cells ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
And Oxidative Stress

Acute lung injury (ALI) is featured by pulmonary edema, alveolar barrier injury, inflammatory response, and oxidative stress. The activation of Sirt1 could relieve lipopolysaccharide- (LPS-) induced murine ALI by maintaining pulmonary epithelial barrier function. Oxypaeoniflorin (Oxy) serves as a major component of Paeonia lactiflora Pall., exerting cardioprotection by activating Sirt1. However, the role of Oxy in ALI induced by LPS remains unclear. The aim of the present study is to illustrate the modulatory effects and molecular mechanisms by which Oxy operates in ALI induced by LPS. The intraperitoneal injection of LPS was performed to establish the murine ALI model while LPS-treated alveolar epithelial cells were used to mimic the in vitro ALI model. Levels of lung injury, oxidative stress, and inflammatory response were detected to observe the potential effects of Oxy on ALI. Oxy treatment mitigated lung edema, inflammatory response, and oxidative stress in mouse response to LPS, apart from improving 7-day survival. Meanwhile, Oxy also increased the expression and activity of Sirt1. Intriguingly, Sirt1 deficiency or inhibition counteracted the protective effects of Oxy treatment in LPS-treated mice or LPS-treated alveolar epithelial cells by regulating the PTEN/AKT signaling pathway. These results demonstrated that Oxy could combat ALI in vivo and in vitro through inhibiting inflammatory response and oxidative stress in a Sirt1-dependent manner. Oxy owns the potential to be a promising candidate against ALI.

scholarly journals Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xin-Yang Wang ◽  
Xin-Yu Li ◽  
Cheng-Hua Wu ◽  
Yu Hao ◽  
Pan-Han Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Tissue Regeneration ◽  
Umbilical Vein ◽  
Endothelial Glycocalyx ◽  
Lipid Mediator ◽  
Protective Effects ◽  
Pulmonary Vascular Permeability

Abstract Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

scholarly journals Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury

2019 ◽  
Vol 20 (7) ◽  
pp. 1678 ◽  
Author(s):  
Yi-Chen Lee ◽  
Chun-Yu Lin ◽  
Yen-Hsu Chen ◽  
Wen-Chin Chiu ◽  
Yen-Yun Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Lines ◽  
Inflammatory Cytokines ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Epithelial Cell Lines ◽  
Nfκb Pathway ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

scholarly journals Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingsong Sun ◽  
Man Luo ◽  
Zhiwei Gao ◽  
Xiang Han ◽  
Weiqin Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interacting Protein ◽  
Wide Range

Abstract Background Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI. Methods We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI. Result TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis. Conclusion OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

High concentration of hydrogen ameliorates lipopolysaccharide-induced acute lung injury in a sirt1-dependent manner

2021 ◽  
pp. 103808
Author(s):  
Junfeng Du ◽  
Jingwen Li ◽  
Rongqin Li ◽  
Xixin Yan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Dependent Manner ◽  
High Concentration

scholarly journals Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model

1999 ◽  
Vol 43 (10) ◽  
pp. 2389-2394 ◽  
Author(s):  
Erika J. Ernst ◽  
Satoru Hashimoto ◽  
Joseph Guglielmo ◽  
Teiji Sawa ◽  
Jean-Francois Pittet ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Rat Model ◽  
In Vivo Model ◽  
Antibiotic Administration ◽  
Lung Water ◽  
Alveolar Epithelial ◽  
The Right

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

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