scholarly journals NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jianhua Huang ◽  
Li Li ◽  
Weifeng Yuan ◽  
Linxin Zheng ◽  
Zhenhui Guo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Binding Domain ◽  
Dependent Manner ◽  
Protective Effects ◽  
Lps Challenge ◽  
Domain Peptide ◽  
Nemo Binding Domain ◽  
Dose Dependent

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-αand NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-αand IL-1βsecretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

scholarly journals NEMO-Binding Domain Peptide Ameliorates Alveolar Hypercoagulation and Fibrinolytic Inhibition in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via NF-κB Signaling Pathway in Mice

2020 ◽  
Author(s):  
Yahui WANG ◽  
Yanqi WU ◽  
Bo LIU ◽  
Huilin YANG ◽  
Hong QIAN ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Signaling Pathway ◽  
Distress Syndrome ◽  
Dependent Manner ◽  
Domain Peptide ◽  
Nemo Binding Domain ◽  
Dose Dependent ◽  
Pai 1 ◽  
Coagulation And Fibrinolysis

Abstract Background It was confirmed that alveolar hypercoagulation and fibrinolytic inhibition were associated with refractory hypoxemia in acute respiratory distress syndrome (ARDS), and NF-κB pathway was involved in this process. The purpose of the present study is to explore the effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBDP) to alleviate alveolar hypercoagulation and fibrinolytic inhibition aroused by lipopolysaccharide in ARDS mice. Materials and Methods Adult male BALB/c mice inhaled lipopolysaccharide (LPS, mg/L) to induce ARDS. 30 minutes before LPS administration, we treated the mice with increasing concentrations of intratracheally inhaled NBDP or saline aerosol. Six hours after LPS treatment, bronchoalveolar lavage fluids (BALF) were collected and then all mice were executed. We checked coagulation and fibrinolysis associated factors in lung tissues and in BALF as well. We simultaneously observed the activation of NF-κB signaling pathway as well. Results NBDP pretreatment dose-dependently inhibited either the expressions of tissue factor (TF) and plasminogen activator inhibitor (PAI) 1 in lung tissues or the secretions of TF, PAI-1, thrombin-antithrombin complex (TAT) and promoted activated protein C (APC) secretion in BALF induced by LPS. LPS-induced high expression of pulmonary procollagen peptide type Ⅲ (PⅢP) was also declined by NBDP pretreatment in dose-dependent manner. Western blotting showed that NBDP pretreatment obviously attenuated LPS-induced IKKα/β, Iκα and NF-κB p65 activation. LPS-induced p65 DNA binding activity was inhibited by NBDP pretreatment either. We also noticed NBDP protected mice against LPS-induced lung injury in a dose-dependent manner.Conclusions Our experimental findings demonstrate that NBDP dose-dependently ameliorated LPS-induced alveolar hypercoagulation and fibrinolytic inhibition through inhibiting NF-κB signaling pathway. NBDP is expected to be a new therapeutic target to correct the abnormalities of alveolar coagulation and fibrinolysis in ARDS.

scholarly journals Seabuckthorn Paste Protects Lipopolysaccharide-Induced Acute Lung Injury in Mice through Attenuation of Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Leilei Du ◽  
Xiaoxin Hu ◽  
Chu Chen ◽  
Tingting Kuang ◽  
Hengfu Yin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Translocation ◽  
Body Weight Loss ◽  
Tibetan Medicine ◽  
Related Factor ◽  
Dependent Manner ◽  
Protective Effects ◽  
Lps Challenge

Oxidative stress is one of the major mechanisms implicated in endotoxin-induced acute lung injury. Seabuckthorn paste (SP), a traditional Tibetan medicine with high content of polyphenols and remarkable antioxidant activity, is commonly used in treating pulmonary diseases. In the present study, the protective effects and possible underlying mechanisms of SP on lipopolysaccharide- (LPS-) induced acute lung injury in mice were investigated. It was found that body weight loss, lung tissue microstructure lesions, transvascular leakage increase, malondialdehyde augmentation, and the reduction of superoxide dismutase and glutathione peroxidase levels caused by LPS challenge were all consistently relieved by SP treatment in a dose-dependent manner. Moreover, accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in lung nuclei caused by SP treatment was observed. Our study demonstrated that SP can provide significant protection against LPS-induced acute lung injury through maintaining redox homeostasis, and its mechanism involves Nrf2 nuclear translocation and activation.

scholarly journals NEMO-Binding Domain Peptide ameliorates alveolar hypercoagulation and fibrinolytic inhibition in lipopolysaccharide-induced acute respiratory distress syndrome via NF-κB signaling pathway in mice

2020 ◽  
Author(s):  
Yahui Wang ◽  
Yanqi Wu ◽  
Bo Liu ◽  
Huilin Yang ◽  
Hong Qian ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Signaling Pathway ◽  
Distress Syndrome ◽  
Dependent Manner ◽  
Domain Peptide ◽  
Nemo Binding Domain ◽  
Dose Dependent ◽  
Pai 1 ◽  
Coagulation And Fibrinolysis

Abstract Background It was confirmed that alveolar hypercoagulation and fibrinolytic inhibition were associated with refractory hypoxemia in acute respiratory distress syndrome (ARDS), and NF-κB pathway was involved in this process. The purpose of the present study is to explore the effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBDP) to alleviate alveolar hypercoagulation and fibrinolytic inhibition aroused by lipopolysaccharide in ARDS mice. Materials and Methods Adult male BALB/c mice inhaled lipopolysaccharide (LPS, mg/L) to induce ARDS. 30 minutes before LPS administration, we treated the mice with increasing concentrations of intratracheally inhaled NBDP or saline aerosol. Six hours after LPS treatment, bronchoalveolar lavage fluids (BALF) were collected and then all mice were executed. We checked coagulation and fibrinolysis associated factors in lung tissues and in BALF as well. We simultaneously observed the activation of NF-κB signaling pathway as well. Results NBDP pretreatment dose-dependently inhibited either the expressions of tissue factor (TF) and plasminogen activator inhibitor (PAI) 1 in lung tissues or the secretions of TF, PAI-1, thrombin-antithrombin complex (TAT) and promoted activated protein C (APC) secretion in BALF induced by LPS. LPS-induced high expression of pulmonary procollagen peptide type Ⅲ (PⅢP) was also declined by NBDP pretreatment in dose-dependent manner. Western blotting showed that NBDP pretreatment obviously attenuated LPS-induced IKKα/β, Iκα and NF-κB p65 activation. LPS-induced p65 DNA binding activity was inhibited by NBDP pretreatment either. We also noticed NBDP protected mice against LPS-induced lung injury in a dose-dependent manner. Conclusions Our experimental findings demonstrate that NBDP dose-dependently ameliorated LPS-induced alveolar hypercoagulation and fibrinolytic inhibition through inhibiting NF-κB signaling pathway. NBDP is expected to be a new therapeutic target to correct the abnormalities of alveolar coagulation and fibrinolysis in ARDS.

scholarly journals Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Junyan Han ◽  
Deshun Ma ◽  
Miao Zhang ◽  
Xuelian Yang ◽  
Dehong Tan
Keyword(s):  
Body Weight ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Sod Activity ◽  
Protein Levels ◽  
Injury Characteristic ◽  
Dose Dependent

The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-αlevels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

scholarly journals Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Quanxin Ma ◽  
Kai Wang ◽  
Qinqin Yang ◽  
Shun Ping ◽  
Weichun Zhao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Folk Medicine ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

scholarly journals Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Qiong He ◽  
Can-Can Zhou ◽  
Jiu-Ling Deng ◽  
Liang Wang ◽  
Wan-Sheng Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Lung Edema ◽  
Protective Effects ◽  
And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

scholarly journals Emodin Attenuates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis Signaling Pathway In vitro and In vivo

Inflammation ◽  
2021 ◽  
Author(s):  
Yuhan Liu ◽  
Luorui Shang ◽  
Jiabin Zhou ◽  
Guangtao Pan ◽  
Fangyuan Zhou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Quantitative Polymerase Chain Reaction ◽  
Interleukin 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects

Abstract—Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1β) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1β, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.

scholarly journals Anti-Inflammatory Effects of Shenfu Injection against Acute Lung Injury through Inhibiting HMGB1-NF-κB Pathway in a Rat Model of Endotoxin Shock

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Liu ◽  
Fei Ai ◽  
Hui Li ◽  
Qin Xu ◽  
Liyan Mei ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Survival Rate ◽  
Lung Injury ◽  
Lung Tissue ◽  
Rat Model ◽  
Endotoxin Shock ◽  
Dependent Manner ◽  
Shenfu Injection ◽  
Anti Inflammatory ◽  
Dose Dependent

Shenfu injection (SFI), a Chinese herbal medicine with substances extracted from Ginseng Radix et Rhizoma Rubra and Aconiti Lateralis Radix Praeparata, is widely used as an anti-inflammatory reagent to treat endotoxin shock in China. However, the mechanism of SFI in endotoxin shock remains to be illuminated. High mobility group box 1 (HMGB1), a vital inflammatory factor in the late stage of endotoxin shock, may stimulate multiple signalling cascades, including κB (NF-κB), a nuclear transcription factor, as well as tumour necrosis factor (TNF)-α and interleukin (IL)-1β, among others in the overexpression of downstream proinflammatory cytokines. An investigation into the effects of SFI on the inhibition of the HMGB1-NF-κB pathway revealed the contribution of SFI to acute lung injury (ALI) in a rat model of endotoxin shock. To assess the anti-inflammatory activity of SFI, 5 ml/kg, 10 ml/kg, or 15 ml/kg of SFI was administered to different groups of rats following an injection of LPS, and the mean arterial pressure (MAP) at 5 h and the survival rate at 72 h were measured. 24 h after LPS injection, we observed pathological changes in the lung tissue and measured the mRNA expression, production, translocation, and secretion of HMGB1, as well as the expression of the NF-κB signal pathway-related proteins inhibitor of NF-κB (IκB)-α, P50, and P65. We also evaluated the regulation of SFI on the secretion of inflammatory factors including interleukin-1 beta (IL-1β) and TNF-α. SFI effectively prevented the drop in MAP, relieved lung tissue damage, and increased the survival rate in the endotoxin shock model in dose-dependent manner. SFI inhibited the transcription, expression, translocation, and secretion of HMGB1, increased the expression of toll-like receptor (TLR4), increased the production of IκB-α, and decreased the levels of P65, P50, and TNF-α in the lung tissue of endotoxin shock rats in a dose-dependent manner. Furthermore, SFI decreased the secretion of proinflammatory cytokines TNF-α and IL-1β. In summary, SFI improves the survival rate of endotoxin shock, perhaps through inhibiting the HMGB1-NF-κB pathway and thus preventing cytokine storm.

scholarly journals Protective effect of adenosine receptors against lipopolysaccharide-induced acute lung injury

2014 ◽  
Vol 306 (6) ◽  
pp. L497-L507 ◽  
Author(s):  
Joyce N. Gonzales ◽  
Boris Gorshkov ◽  
Matthew N. Varn ◽  
Marina A. Zemskova ◽  
Evgeny A. Zemskov ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Adenosine Receptors ◽  
Blue Dye ◽  
Protective Effects ◽  
Extracellular Adenosine ◽  
Lps Challenge ◽  
Cell Counts ◽  
The Usa

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) affect 200,000 people a year in the USA. Pulmonary vascular and specifically endothelial cell (EC) barrier compromise is a hallmark of these diseases. We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. On the basis of these data, we hypothesized that activation of ARs might exert barrier-protective effects in a model of ALI/ARDS in mice. To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N-ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. Postexperiment cell counts, Evans Blue Dye albumin (EBDA) extravasation, levels of proteins, and inflammatory cytokines were analyzed. Harvested lungs were used for histology and myeloperoxidase studies. Mice challenged with LPS alone demonstrated an inflammatory response typical of ALI. Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. Histology displayed reduced infiltration of neutrophils. NECA had a similar effect on LPS-induced vascular barrier compromise. Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. Furthermore, adenosine significantly attenuated protein degradation of A2A and A3 receptors induced by LPS. Collectively, our results demonstrate that activation of ARs protects and restores vascular barrier functions and reduces inflammation in LPS-induced ALI.

Sign in / Sign up

Export Citation Format

Share Document