scholarly journals Angelica Polysaccharide Ameliorates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 and NF-κB Signaling Pathways in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yan Zhu ◽  
Taocheng Meng ◽  
Aichen Sun ◽  
Jintao Li ◽  
Jinlai Li
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathways ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Receptor Protein ◽  
Lung Edema ◽  
Caspase 1 ◽  
Tnf Α

Objective. This study aimed to explore the role of angelica polysaccharide (AP) in sepsis-induced acute lung injury (ALI) and its underlying molecular mechanism. Methods. A sepsis model of cecal ligation and puncture (CLP) in male BALB/C mice was used. Then, 24 h after CLP, histopathological changes in lung tissue, lung wet/dry weight ratio, and inflammatory cell infiltration were analyzed. Next, levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18), as well as the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH), were measured to assess the role of AP. The protein expression of NF-κB p65, p-NF-κB p65, IκBα, p-IκBα, nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3), ASC, and caspase-1 was detected by western blot. In addition, the expression of p-NF-κB p65 and NLRP3 was detected by immunohistochemistry. Results. AP treatment ameliorated CLP-induced lung injury and lung edema, as well as decreased the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). AP reduced the levels of TNF-α, IL-1β, IL-6, and IL-18 in BALF, as well as in serum. Moreover, AP decreased MPO activity and MDA content, whereas increased SOD and GSH levels. AP inhibited the expression of p-NF-κB p65, p-IκBα, NLRP3, ASC, and caspase-1, while promoted IκBα expression. Conclusion. This study demonstrated that AP exhibits protective effects against sepsis-induced ALI by inhibiting NLRP3 and NF-κB signaling pathways in mice.

scholarly journals MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

2021 ◽  
Vol 49 (5) ◽  
pp. 117-124
Author(s):  
Wenmei Liang ◽  
Li Guo ◽  
Tonghua Liu ◽  
Song Qin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Tunel Staining ◽  
Cecal Ligation And Puncture ◽  
Tnf Α ◽  
Factor Α

Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

scholarly journals Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury

2016 ◽  
Vol 311 (2) ◽  
pp. L517-L524 ◽  
Author(s):  
Kaiser M. Bijli ◽  
Fabeha Fazal ◽  
Spencer A. Slavin ◽  
Antony Leonard ◽  
Valerie Grose ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Phospholipase C ◽  
Phorbol Esters ◽  
Critical Determinant ◽  
Monocyte Chemoattractant Protein 1 ◽  
Barrier Disruption ◽  
Proinflammatory Mediators ◽  
Tnf Α

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε−/− mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε−/− mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε+/+ mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI.

YiQiFuMai Lyophilized Injection Attenuates Sepsis-Induced Acute Lung Injury via TLR4/Src/VE-cadherin/p120-catenin Signaling Pathway

2020 ◽  
Author(s):  
Xue-wei Pan ◽  
Li-xuan Xue ◽  
Qian-liu Zhou ◽  
Jia-zhi Zhang ◽  
Yu-jie Dai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Cecal Ligation ◽  
Inflammatory Cells ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Lung Edema ◽  
P120 Catenin

Abstract Background: Sepsis is a severe disorder leading to a clinically critical syndrome of multiple organ dysfunction syndrome. Most patients with sepsis will be associated with acute lung injury (ALI), which is an independent risk factors of organ failure and death in patients with sepsis at the same time. YiQiFuMai Lyophilized Injection (YQFM) is a modern traditional Chinese prescription preparation, which could ameliorate ALI induced by lipopolysaccharide (LPS) or fine particulate matter. The current study aimed to investigate the effect of YQFM on sepsis-induced ALI and the underlying mechanism.Methods: Male C57BL/6J mice were treated with cecal ligation and puncture (CLP) after tail intravenous injected with YQFM (1, 2 and 4 g/kg). The measurements of lung edema, evans blue leakage, myeloperoxidase content, inflammatory cells in bronchoalveolar lavage fluid, histopathological assay and expression of associated proteins were performed at 18 h after CLP.Results: The results illustrated that YQFM inhibited pulmonary edema and inflammatory response, thus ameliorated ALI in sepsis mice. Furthermore, the expression of TLR4 and phosphorylated Src was down-regulated, and the expression of p120-catenin and VE-cadherin was restored by YQFM administration.Conclusion: Our study suggested the therapeutic potential of YQFM on treating sepsis-induced ALI via regulating TLR4/Src/VE-cadherin/p120-catenin signaling pathway.

scholarly journals Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Shuiqiao Fu ◽  
Weina Lu ◽  
Wenqiao Yu ◽  
Jun Hu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Cordyceps Sinensis ◽  
Myeloperoxidase Activity ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tnf Α ◽  
Cox 2

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

Shen-Fu Attenuates Endotoxin-Induced Acute Lung Injury in Rats

2006 ◽  
Vol 34 (04) ◽  
pp. 613-621 ◽  
Author(s):  
Yanning Qian ◽  
Jie Sun ◽  
Zhongyun Wang ◽  
Jianjun Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nf Kappa B ◽  
Lung Weight ◽  
Tnf Α ◽  
Male Wistar Rats

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

scholarly journals Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Limei Wan ◽  
Weibin Wu ◽  
Shunjun Jiang ◽  
Shanhe Wan ◽  
Dongmei Meng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Calcium Channel ◽  
Lavage Fluid ◽  
Cell Number ◽  
Effector Cells ◽  
Potent Inhibition ◽  
Tnf Α ◽  
Calcium Channel Inhibitors

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

scholarly journals A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits

Gut ◽  
1998 ◽  
Vol 43 (2) ◽  
pp. 232-239 ◽  
Author(s):  
M O Osman ◽  
J U Kristensen ◽  
N O Jacobsen ◽  
S B Lausten ◽  
B Deleuran ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Necrosis ◽  
Interleukin 8 ◽  
Systemic Complications ◽  
Duct Ligation ◽  
Tnf Α

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

scholarly journals Novel Insights Into Phosgene-Induced Acute Lung Injury in Rats: Role of Dysregulated Cardiopulmonary Reflexes and Nitric Oxide in Lung Edema Pathogenesis

2012 ◽  
Vol 131 (2) ◽  
pp. 612-628 ◽  
Author(s):  
Wenli Li ◽  
Fangfang Liu ◽  
Chen Wang ◽  
Hubert Truebel ◽  
Juergen Pauluhn
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Edema

scholarly journals Comparison of direct and indirect models of early induced acute lung injury

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Laura Chimenti ◽  
Luis Morales-Quinteros ◽  
Ferranda Puig ◽  
Marta Camprubi-Rimblas ◽  
Raquel Guillamat-Prats ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Acute Phase ◽  
Cecal Ligation ◽  
Sprague Dawley ◽  
Acid Aspiration ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Gastric Contents ◽  
Bacterial Superinfection

Abstract Background The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. Aim To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Materials and methods Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. Results At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Conclusions Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI.

scholarly journals miR-20a attenuates acute lung injury in septic rats via targeting TLR4

2021 ◽  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Cecal Ligation ◽  
Normal Group ◽  
Lung Damage ◽  
Luciferase Reporter ◽  
Arterial Bleeding ◽  
Tnf Α

Background: Sepsis is most likely to cause lung damage in patients, and the detection rate and mortality rate are high. Here, we investigated the expression of miR-20a in sepsis-induced acute lung injury (ALI) rats and its effect on inflammatory response, and reveal its possible molecular mechanism. Method: The model of acute lung injury caused by sepsis in rats was established by cecal ligation and puncture. The expression of miR-20a in lung tissue was determined by RT-qPCR. Acute lung injury rats were injected with 5 nmol miR-20a agomir or agomir NC every day for 3 days. Rats were sacrificed by arterial bleeding and lung tissues were removed. Serum interleukin (IL) -1β, IL-6, and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE staining was used to observe the pathology of lung tissue and calculate the pathological score of lung injury. Western blot to determine the level of TLR4 and nuclear transcription factor κB p65 (NF-κB p65) protein in lung tissue. The luciferase reporter assay was used to verify the binding effect of miR-20a on the 3 non-coding TLR4. Results: We found that compared with that in Normal group, the expression of miR-20a in lung tissues of rats with ALI was decreased (p < 0.05). In miR-20a agomir group, the plasma level of IL-1β, IL-6, and TNF-α was significantly lower than that in agomir NC group and ALI group (p < 0.05), while higher than those in Normal group (p < 0.05). The HE staining results showed that the pathological score of lung injury in rats in miR-20a agomir group was lower than that of agomir NC group and ALI group (p < 0.05). Compared with agomir NC group and ALI group, the expression of TLR4 and NF-κB p65 in miR-20a agomir group was decreased (p < 0.01). The luciferase reporting experiment confirmed that TLR4 was a target gene of miR-20a. Conclusion: To sum up, miR-20a exerts a protective effect on sepsis-induced ALI rats through its anti-inflammatory effect. The targeting of TLR4 by miR-20a may be an effective method to reduce the inflammatory response in sepsis-induced ALI.

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