Edaravone attenuates lipopolysaccharide-induced acute respiratory distress syndrome associated early pulmonary fibrosis via amelioration of oxidative stress and transforming growth factor-β1/Smad3 signaling

Wang, Xida; Lai, Rongde; Su, Xiangfen; Chen, Guibin; Liang, Zijing

doi:10.1016/j.bbrc.2017.10.165

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…The present study indicated that TGF-β1 is activated in the early stage of ARDS and participates in the process of lung tissue damage repair. As a potent profibrotic cytokine, it regulates the expression and secretion of collagen in lung tissue (13). The present study indicated that MRC-5 cells treated with different concentrations of LPS expressed different levels of TGF-β1 mRNA and Col1α1 mRNA.…”

Section: Discussionmentioning

confidence: 50%

Mechanical stretch and LPS affect the proliferation, extracellular matrix remodeling and viscoelasticity of lung fibroblasts

et al. 2020

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The present study aimed to investigate the effects of mechanical stretch and lipopolysaccharides (LPS) on the expression of transforming growth factor-β1 (TGF-β1) and collagen and viscoelasticity in human embryonic MRC-5 lung fibroblasts cultured in vitro and to assess the mechanisms of ARDS-associated ventilator-induced lung injury using an in vitro model. Human embryonic MRC-5 lung fibroblasts were treated with different concentrations of LPS to establish an acute respiratory distress syndrome (ARDS) cell injury model, followed by further culture under different mechanical stretch amplitudes using the Flexcell system to establish a cellular mechanical damage model. The proliferation of MRC-5 cells and the protein and gene expression levels of TGF-β1 and collagen were detected by flow cytometry, ELISA and reverse transcription-quantitative PCR, respectively. As the concentration of LPS increased, the proliferation activity of MRC-5 cells gradually decreased. Low concentrations of LPS led to upregulation of the secretion levels of TGF-β1 and collagen I and the expression of their mRNA, TGF-β1 mRNA and collagen type 1, α1. Conversely, high concentrations of LPS reduced TGF-β1 and collagen I levels and their gene expression. Mechanical stimulation with a stretch of 5% increased the cell proliferation activity; however, it had no significant effect on the expression levels of TGF-β1 and collagen. Mechanical stimulation with a stretching force of 10% inhibited the cell proliferation but increased the expression levels of TGF-β1 and collagen I. A higher mechanical stimulation (15 and 20%) had a significantly greater effect. Mechanical stretch and LPS stimulation led to changes in the structure and viscoelastic behavior of human embryonic MRC-5 lung fibroblasts. In terms of cell function, mechanical stretch may cause an increase in the expression of TGF-β1 in MRC-5 cells, in turn affecting the transcription and translation of collagen genes. This present study provides provides cell-level evidence for understand the mechanisms of action behind the ARDS ventilator-induced lung injury and lung structural remodeling.

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Section: Discussionmentioning

confidence: 50%

Mechanical stretch and LPS affect the proliferation, extracellular matrix remodeling and viscoelasticity of lung fibroblasts

et al. 2020

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“…ROS acts as second messenger to drive inflammasome activation and has been identified as an important mechanism for NLRP3 inflammasome activation [47] and is believed to be a common NLR/caspase-1 complex activator, which mediates pyroptosis [48]. Under normal conditions, the antioxidant enzymes can eliminate ROS during cell metabolism to maintain a balance of ROS generation and elimination [49]. When ROS accumulates ceaselessly and endogenic antioxygen defence system cannot eliminate it in time, it induces oxidative stress, cellular disorders including upregulated lipid peroxidation, and cell apoptosis [50].…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes

Qiu

Ming

et al. 2019

Journal of Diabetes Research

261

146

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Diabetes aggravates myocardial ischemia-reperfusion (I/R) injury because of the combination effects of changes in glucose and lipid energy metabolism, oxidative stress, and systemic inflammatory response. Studies have indicated that myocardial I/R may coincide and interact with sepsis and inflammation. However, the role of LPS in hypoxia/reoxygenation (H/R) injury in cardiomyocytes under high glucose conditions is still unclear. Our objective was to examine whether lipopolysaccharide (LPS) could aggravate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by upregulating ROS production to activate NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. H9C2 cardiomyocytes were exposed to HG (30 mM) condition with or without LPS, along with caspase-1 inhibitor (Ac-YVAD-CMK), inflammasome inhibitor (BAY11-7082), ROS scavenger N-acetylcysteine (NAC), or not for 24 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). The cell viability, lactate dehydrogenase (LDH) release, caspase-1 activity, and intracellular ROS production were detected by using assay kits. The incidence of pyroptosis was detected by calcein-AM/propidium iodide (PI) double staining kit. The concentrations of IL-1β and IL-18 in the supernatants were assessed by ELISA. The mRNA levels of NLRP3, ASC, and caspase-1 were detected by qRT-PCR. The protein levels of NF-κB p65, NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18 were detected by western blot. The results indicated that pretreatment LPS with 1 μg/ml not 0.1 μg/ml could efficiently aggravate HG and H/R injury by activating NLRP3 inflammasome to mediate pyroptosis in H9C2 cells, as evidenced by increased LDH release and decreased cell viability in the cells, and increased expression of NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18. Meanwhile, Ac-YVAD-CMK, BAY11-7082, or NAC attenuated HG- and H/R-induced H9C2 cell injury with LPS stimulated by reversing the activation of NLRP3 inflammasome-mediated pyroptosis. In conclusion, LPS could increase the sensitivity of H9C2 cells to HG and H/R and aggravated HG- and H/R-induced H9C2 cell injury by promoting ROS production to induce NLRP3 inflammasome-mediated pyroptosis.

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“…They have also been recognized to play an essential role in NLRP3 inflammasome activation (52) and drive NLRP3/caspase-1 complex activation, leading to pyroptosis (53). Under physiological conditions, ROS are eliminated by antioxidant enzymes during cell metabolism, maintaining the balance between ROS generation and elimination (54). When ROS are continuously generated, the intracellular antioxidant defense systems cannot maintain redox homeostasis, which eventually leads to oxidative stress-induced injury and cellular damage, including cell apoptosis (55) and vascular endothelial cell pyroptosis (21,56).…”

Section: Discussionmentioning

confidence: 99%

Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes

Su¹,

Wei²,

Fu³

et al. 2021

Ann Transl Med

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Background: Melatonin (MT) has been shown to protect against various cardiovascular diseases. However, the effect of MT on lipopolysaccharide (LPS)-induced myocardial injury is poorly understood. This study aims to evaluate the effects of MT on LPS-induced myocardial injury in vitro.Methods: H9C2 cells were divided into a control group, MT group, LPS group, and MT + LPS group.The control group was treated with sterile saline solution, the LPS group received 8 μg/mL LPS for 24 h, MT + LPS cells were pretreated with 200 μmol/L MT for 2 h then with 8 μg/mL LPS for 24 h, and the MT group received only 200 μmol/L MT for 2 h. The CCK-8 assay and lactate dehydrogenase (LDH) activity assay were used to analyze cell viability and LDH release, respectively. Intracellular reactive oxygen species (ROS) and the rate of pyroptosis were measured using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and propidium iodide (PI) staining, respectively. The cell supernatants were used to measure the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1β by enzyme-linked immunosorbent assay (ELISA). The protein levels of iNOS, COX-2, NF-κB, p-NF-κB, NLRP3, caspase-1, and GSDMD were detected by western blot.Results: MT pretreatment significantly improved LPS-induced myocardial injury by inhibiting inflammation and pyroptosis in H9C2 cells. Moreover, MT inhibited the activation of the NF-κB pathway, and reduced the expression of inflammation-related proteins (iNOS and COX-2), and pyroptosis-related proteins (NLRP3, caspase-1, and GSDMD).Conclusions: Our data suggests that MT can alleviate LPS-induced myocardial injury, providing novel insights into the treatment of sepsis-induced myocardial dysfunction.

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Edaravone attenuates lipopolysaccharide-induced acute respiratory distress syndrome associated early pulmonary fibrosis via amelioration of oxidative stress and transforming growth factor-β1/Smad3 signaling

Cited by 13 publications

References 31 publications

Mechanical stretch and LPS affect the proliferation, extracellular matrix remodeling and viscoelasticity of lung fibroblasts

Mechanical stretch and LPS affect the proliferation, extracellular matrix remodeling and viscoelasticity of lung fibroblasts

Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes

Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes

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