scholarly journals Baicalin exerts protective effects against lipopolysaccharide-induced acute lung injury by regulating the crosstalk between the CX3CL1-CX3CR1 axis and NF-κB pathway in CX3CL1-knockout mice

2016 ◽  
Vol 37 (3) ◽  
pp. 703-715 ◽  
Author(s):  
XIN-MIN DING ◽  
LEI PAN ◽  
YONG WANG ◽  
QIN-ZHI XU
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Protective Effects

scholarly journals Atrial natriuretic peptide attenuates LPS-induced lung vascular leak: role of PAK1

2010 ◽  
Vol 299 (5) ◽  
pp. L652-L663 ◽  
Author(s):  
Anna A. Birukova ◽  
Junjie Xing ◽  
Panfeng Fu ◽  
Bakhtiyor Yakubov ◽  
Oleksii Dubrovskyi ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Atrial Natriuretic Peptide ◽  
Bronchoalveolar Lavage ◽  
Knockout Mice ◽  
Endothelial Barrier ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Vascular Leak ◽  
Evans Blue Extravasation

Increased levels of atrial natriuretic peptide (ANP) in the models of sepsis, pulmonary edema, and acute respiratory distress syndrome (ARDS) suggest its potential role in the modulation of acute lung injury. We have recently described ANP-protective effects against thrombin-induced barrier dysfunction in pulmonary endothelial cells (EC). The current study examined involvement of the Rac effector p21-activated kinase (PAK1) in ANP-protective effects in the model of lung vascular permeability induced by bacterial wall LPS. C57BL/6J mice or ANP knockout mice (Nppa−/−) were treated with LPS (0.63 mg/kg intratracheal) with or without ANP (2 μg/kg iv). Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, Evans blue extravasation, and lung histology. Endothelial barrier properties were assessed by morphological analysis and measurements of transendothelial electrical resistance. ANP treatment stimulated Rac-dependent PAK1 phosphorylation, attenuated endothelial permeability caused by LPS, TNF-α, and IL-6, decreased LPS-induced cell and protein accumulation in bronchoalveolar lavage fluid, and suppressed Evans blue extravasation in the murine model of acute lung injury. More severe LPS-induced lung injury and vascular leak were observed in ANP knockout mice. In rescue experiments, ANP injection significantly reduced lung injury in Nppa−/− mice caused by LPS. Molecular inhibition of PAK1 suppressed the protective effects of ANP treatment against LPS-induced lung injury and endothelial barrier dysfunction. This study shows that the protective effects of ANP against LPS-induced vascular leak are mediated at least in part by PAK1-dependent signaling leading to EC barrier enhancement. Our data suggest a direct role for ANP in endothelial barrier regulation via modulation of small GTPase signaling.

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.

Protective effects of coumestrol on lipopolysaccharide-induced acute lung injury via the inhibition of proinflammatory mediators and NF-κB activation

2017 ◽  
Vol 34 ◽  
pp. 181-188 ◽  
Author(s):  
Heung Joo Yuk ◽  
Jae Won Lee ◽  
Hyun Ah Park ◽  
Ok-Kyoung Kwon ◽  
Kyeong-Hwa Seo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effects ◽  
Proinflammatory Mediators

scholarly journals Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

2007 ◽  
Vol 13 (46) ◽  
pp. 6172 ◽  
Author(s):  
Oge Tascilar ◽  
Güldeniz Karadeniz Cakmak ◽  
Ishak Ozel Tekin ◽  
Ali Ugur Emre ◽  
Bulent Hamdi Ucan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Rat Model ◽  
Necrotizing Pancreatitis ◽  
Acute Necrotizing Pancreatitis ◽  
Protective Effects ◽  
Acute Necrotizing

scholarly journals Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu-bao Qiu ◽  
Bin-bin Wan ◽  
Gang Liu ◽  
Ya-xian Wu ◽  
Dan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Lipid Peroxide ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Glutathione Depletion ◽  
Stress Injury ◽  
Nrf2 Knockout

Abstract Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. Methods we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. Conclusions These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.

scholarly journals Corrigendum to “JAK2/STAT3 Pathway Was Associated with the Protective Effects of IL-22 on Aortic Dissection with Acute Lung Injury”

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Wei Ren ◽  
Zhiwei Wang ◽  
Zhiyong Wu ◽  
Zhipeng Hu ◽  
Feifeng Dai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Aortic Dissection ◽  
Protective Effects ◽  
Stat3 Pathway

Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice

2013 ◽  
Vol 58 ◽  
pp. 133-140 ◽  
Author(s):  
Yan Chen ◽  
Yi-chu Nie ◽  
Yu-long Luo ◽  
Feng Lin ◽  
Yan-fang Zheng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Protective Effects

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 Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Lisa E. Gralinski ◽  
Armand Bankhead ◽  
Sophia Jeng ◽  
Vineet D. Menachery ◽  
Sean Proll ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Disease Severity ◽  
Knockout Mice ◽  
Differentially Expressed ◽  
Lung Pathology ◽  
Priority List ◽  
Disease Outcomes ◽  
Pathological Disease

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. IMPORTANCE Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI.

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