Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF‐κB signaling pathway in vivo and in vitro

2019 ◽  
Vol 120 (6) ◽  
pp. 8956-8964 ◽  
Author(s):  
XingXing Hu ◽  
Shang Liu ◽  
Jin Zhu ◽  
HaiBin Ni
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Dachengqi Decoction

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 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.

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 Hydrogen-Rich Saline Inhibits Lipopolysaccharide-Induced Acute Lung Injury and Endothelial Dysfunction by Regulating Autophagy through mTOR/TFEB Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Zhiling Fu ◽  
Ze Zhang ◽  
Xiuying Wu ◽  
Jin Zhang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antioxidative Stress ◽  
Related Proteins ◽  
The Relationship ◽  
Apoptosis Proteins

Background. Hydrogen-rich saline (HRS) has strong anti-inflammatory, antioxidative stress, and antiapoptotic properties. The study focused on the protection of HRS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rat models and the relationship with autophagic regulation and mTOR/TFEB signaling pathway. Material and Methods. The LPS-induced ALI rats’ model was established. Pathohistological change in lung tissue was detected by hematoxylin-eosin staining. The inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The key apoptosis proteins and autophagy-relevant proteins were analyzed by western blotting. In vitro, HPMEC models of ALI were treated with LPS. The inflammatory cytokines were detected. Apoptosis rate was determined by flow cytometry. The autophagy and mTOR/TFEB signaling pathway-related proteins were detected by western blot and immunohistochemical staining. Results. HRS attenuated LPS-induced ALI and apoptosis both in vivo and in vitro. HRS attenuated inflammatory response, inhibited apoptosis, induced and activated autophagy in LPS-induced ALI model, and downregulated mTOR/TFEB signaling pathway. The protection of HRS can be blocked by autophagy inhibitor. Moreover, mTOR activator reversed HRS protection and mTOR inhibitor enhanced HRS protection in LPS-induced model and HRS activated autophagy via mTOR/TFEB signaling pathway. Conclusion. The results confirmed the protection of HRS in LPS-induced ALI by regulating apoptosis through inhibiting the mTOR/TFEB signaling pathway.

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.

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via NF-κB Signaling Pathway in vivo and in vitro

Inflammation ◽  
2017 ◽  
Vol 40 (4) ◽  
pp. 1111-1122 ◽  
Author(s):  
Xiaofeng Niu ◽  
Fang Liu ◽  
Weifeng Li ◽  
Wenbing Zhi ◽  
Hailin Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway

scholarly journals Epigallocatechin-3-gallate Ameliorates Seawater Aspiration-Induced Acute Lung Injury via Regulating Inflammatory Cytokines and Inhibiting JAK/STAT1 Pathway in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Wei Liu ◽  
Mingqing Dong ◽  
Liyan Bo ◽  
Congcong Li ◽  
Qingqing Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Protein Level ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Signal Transducers ◽  
Phosphorylated Protein

Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-αand IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-αand IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1in vivoandin vitroand reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.

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.

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