scholarly journals Baicalin Magnesium Salt Attenuates Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting of TLR4/NF-κB Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lin Zhang ◽  
Lukun Yang ◽  
Xiaowei Xie ◽  
Hongyue Zheng ◽  
Hangsheng Zheng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Water Soluble ◽  
Magnesium Salt ◽  
Scutellaria Baicalensis Georgi ◽  
Cell Counts

Baicalin (BA) magnesium salt (BA-Mg) is a good water-soluble ingredient extracted from Scutellaria baicalensis Georgi, a commonly used traditional Chinese medicine. This study is aimed at investigating whether BA-Mg could exert a better protective effect on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and illuminate the underlying mechanisms in vivo and in vitro. Mice were intraperitoneally administrated with equimolar BA-Mg, BA, and MgSO4 before LPS inducing ALI. Lung tissues and bronchoalveolar lavage fluid were collected for lung wet/dry ratio, histological examinations, cell counts, and biochemical analyses at 48 h post-LPS exposure. Meanwhile, the protein expressions of TLR4/NF-κB signaling pathway and proinflammatory cytokines in lung tissues and lung bronchial epithelial cells (BEAS-2B) were detected. The results showed BA-Mg pronouncedly ameliorated LPS-induced inflammatory response and histopathological damages, elevated antioxidant enzyme activity (SOD), and downregulated myeloperoxidase (MPO) and malonaldehyde (MDA) levels through the inhibition of TLR4/NF-κB signaling pathway activation. Moreover, the effect of BA-Mg was significantly better than that of BA and MgSO4 in ameliorating symptoms. Overall, BA-Mg can effectively relieve inflammatory response and oxidative stress triggered by LPS, indicating it may be a potential therapeutic candidate for treating ALI.

scholarly journals GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Tao Zhu ◽  
Changyi Li ◽  
Xue Zhang ◽  
Chunyan Ye ◽  
Shuo Tang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Pulmonary Inflammation ◽  
Protein A ◽  
Insulin Level ◽  
Underlying Mechanism ◽  
Ultrastructural Changes

The reduction of pulmonary surfactant (PS) is essential for decreased pulmonary compliance and edema in acute lung injury (ALI). Thyroid transcription factor-1 (TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the most abundant protein component of PS. Simultaneously, the glucagon-like peptide-1 (GLP-1) analogue can enhance SP-A expression in the lung. However, the underlying mechanism is still unknown. The purpose of this study was to explore whether liraglutide, a GLP-1 analogue, upregulates SP-A expression through the TTF-1 signaling pathway in ALI. In vivo, a murine model of ALI was induced by lipopolysaccharide (LPS). Pulmonary inflammation, edema, insulin level, ultrastructural changes in type II alveolar epithelial (ATII) cells, and SP-A and TTF-1 expression were analyzed. In vitro, rat ATII cells were obtained. SP-A and TTF-1 expression in cells was measured. ShRNA-TTF-1 transfection was performed to knock down TTF-1 expression. Our data showed that LPS-induced lung injury and increase in insulin level, and LPS-induced reduction of SP-A and TTF-1 expression in both the lung and cells, were significantly compromised by liraglutide. Furthermore, we also found that these effects of liraglutide were markedly blunted by shRNA-TTF-1. Taken together, our findings suggest that liraglutide enhances SP-A expression in ATII cells and attenuates pulmonary inflammation in LPS-induced ALI, most likely through the TTF-1 signaling pathway.

scholarly journals Osthole Protects against Acute Lung Injury by Suppressing NF-κB-Dependent Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yiyi Jin ◽  
Jianchang Qian ◽  
Xin Ju ◽  
Xiaodong Bao ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Peritoneal Macrophages ◽  
Anti Inflammatory

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

scholarly journals TGF-β-R2 is required for HBP induced acute lung injury and vascular leakage for TGF-[beta]/Smad/Rho signaling pathway activation

2022 ◽  
Author(s):  
Zixuan Liu ◽  
Mingming Chen ◽  
Yini Sun ◽  
Xu Li ◽  
Liu Cao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Vascular Leakage ◽  
Polymorphonuclear Neutrophils ◽  
Heparin Binding

Heparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils (PMNs) participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis, which is related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as one of the primary target sites. However, it is still unclear whether HBP-binding protein receptors exist on the surface of ECs. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro study. We demonstrated that HBP bound to transforming growth factor-β receptor type 2 (TGF-β-R2) as a ligand. GST pull-down analysis reveals that HBP mainly interacts with the extracellular domain of TGF-β-R2. HBP induced acute lung injury (ALI) and vascular leakage via activation of TGF-β/SMAD2/3 signaling pathway. Permeability assay suggests TGF-β-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-β-R2 in the blood-gas barrier in the pathogenesis of HBP-related ALI.

miR-138-5p targets sirtuin1 to regulate acute lung injury by regulation of the NF-κB signaling pathway

2020 ◽  
Vol 98 (8) ◽  
pp. 522-530
Author(s):  
Yinshan Wu ◽  
Weiliang Jiang ◽  
Zhuhua Lu ◽  
Wei Su ◽  
Nan Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Luciferase Assay ◽  
Promote Cell Proliferation ◽  
Pulmonary System ◽  
Pulmonary Inflammatory Response

Acute lung injury (ALI), a disease with a high mortality rate, is a noncardiogenic pulmonary inflammatory response and characterized by damage to the pulmonary system. In this study, we explored the mechanism of the occurrence and development of ALI. It was firstly found that miR-138-5p could inhibit the expression of sirtuin1 (SIRT1), and we further demonstrated that miR-138-5p targets directly SIRT1 through the luciferase assay, while the latter negatively regulated the expression of NF-κB. A549 cells were treated with lipopolysaccharide in vitro to simulate ALI cells and induce ALI in the model mice. The results showed that inhibiting the expression of miR-138-5p could effectively increase the viability of damaged cells, promote cell proliferation, reduce apoptosis, inhibit the inflammatory response, reduce oxidative stress, and then relieve ALI symptoms. Collectively, our results suggested that miR-138-5p can inhibit SIRT1 expression and indirectly activate the NF-κB signaling pathway, thus regulating the development of ALI.

scholarly journals Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Deqiang Luo ◽  
Wei Dai ◽  
Xiaojin Feng ◽  
Chengzhi Ding ◽  
Qiang Shao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Luciferase Reporter ◽  
Lung Pathology ◽  
Caspase 1

AbstractAcute lung injury (ALI) is a common lung pathology that is accompanied by alveolar macrophage (AM) activation and inflammatory response. This study investigated the role of the long non-coding RNA NONRATT004344 (hereafter named lncRNA NLRP3) in regulating the Nod-like receptor protein 3 (NLRP3)-triggered inflammatory response in early ALI and the underlying mechanism as well. We established LPS-induced ALI models to explore their interactive mechanisms in vitro and in vivo. Luciferase reporter assays were performed to determine that miR-138-5p could bind to lncRNA NLRP3 and NLRP3. We observed increased lncRNA NLRP3 expression, decreased miR-138-5p expression, NLRP3 inflammasome activation, and upregulated caspase-1, IL-1β, and IL-18 expression in the LPS-induced ALI model. Furthermore, lncRNA NLRP3 overexpression activated the NLRP3 inflammasome and promoted IL-1β and IL-18 secretion; the miR-138-5p mimic abolished these effects in vivo and in vitro. Consistently, miR-138-5p inhibition reversed the effects of lncRNA NLRP3 silencing on the expression of NLRP3-related molecules and inhibition of the NLRP3/caspase-1/IL-1β signalling pathway. Mechanistically, lncRNA NLRP3 sponging miR-138-5p facilitated NLRP3 activation through a competitive endogenous RNA (ceRNA) mechanism. In summary, our results suggested that lncRNA NLRP3 binding miR-138-5p promotes NLRP3-triggered inflammatory response via lncRNA NLRP3/miR-138-5p/NLRP3 ceRNA network (ceRNET) and provides insights into the treatment of early ALI.

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.

ID: 109: PARKIN MEDIATES ENDOTHELIAL PRO-INFLAMMATORY RESPONSES IN ACUTE LUNG INJURY

2016 ◽  
Vol 64 (4) ◽  
pp. 963.1-963
Author(s):  
E Letsiou ◽  
H Wang ◽  
P Belvitch ◽  
S Dudek ◽  
S Sammani
Keyword(s):  
Acute Lung Injury ◽  
Endothelial Dysfunction ◽  
Lung Injury ◽  
Kinase Inhibitor ◽  
Inflammatory Responses ◽  
Neutrophil Adhesion ◽  
Protein Levels ◽  
Cell Counts

IntroductionAcute lung injury (ALI) and its more severe form, the Acute Respiratory Distress Syndrome (ARDS), are serious conditions resulting from direct or indirect lung injury that occur in critically ill patients and are associated with an unacceptable mortality of up to 40%. A key biological event in the pathogenesis of ALI/ARDS is the dysfunction of the lung endothelium (EC), which is triggered by a variety of inflammatory insults leading to damaged EC, vascular leak, and excessive inflammation. Recently, we demonstrated that an Abl family tyrosine kinase inhibitor, imatinib, protects against LPS-induced endothelial dysfunction by inhibiting c-Abl kinase through mechanisms that remain largely unknown. In the present study, we identified parkin, a novel c-Abl substrate, as a critical mediator of endothelial dysfunction in ALI.MethodsIn vitro Human pulmonary artery endothelial cells (EC) were transfected with siRNA for parkin and then challenged with LPS (1 µg/ml, 3 hrs). Inflammatory mediators were determined in cell lysates and supernatants by Western blotting and ELISA respectively. In vivo C57BL/6 (WT) and parkin deficient (PARK2 KO) male mice (8–12 wks, n=5–8) were subjected to LPS (intratracheally, 1 mg/kg) or PBS (controls), and allowed to recover prior to harvest 18 hrs later. Leakage of proteins into the alveolar space was assessed by measuring the protein levels in the bronchoalveolar lavage (BAL). To assess lung inflammation, neutrophil cell counts, myeloperoxidase (MPO) activity, and IL-6 levels were determined in BAL.ResultsIn human lung EC, down-regulation of parkin by siRNA reduces LPS-induced VCAM-1 expression (adhesion molecule involved in neutrophil adhesion to EC) (by 35%, p<0.05), IL-8 (neutrophil chemoattractant) (by 59%, p<0.01), and IL-6 (inflammatory cytokine) release (by 79%, p<0.01). PARK2 KO mice exhibit less ALI after LPS compared to WT. In PARK2 KO, BAL protein levels were reduced by 27% (p=0.0024) compared to WT mice. LPS-induced neutrophil recruitment into the alveoli of PARK2 KO was attenuated by 47% compared to WT (p=0.0019). BAL MPO activity (marker of neutrophil activation) and BAL IL-6 levels were also significantly lower in PARK2 KO by 52% (p=0.03) and 28% (p=0.0061) respectively.ConclusionThese results suggest that endothelial parkin mediates EC activation and neutrophil adhesion/migration after LPS, and therefore it may represent a new potential therapeutic target in ALI/ARDS.

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.

Sign in / Sign up

Export Citation Format

Share Document