Endoplasmic reticulum stress and acute lung injury

BACKGROUND: Circular RNAs (circRNAs) have been reported to be involved in the pathophysiology of sepsis-induced acute lung injury (sepsis-ALI). Herein, this work aimed to investigate the role and mechanism of circWDR33 in the process of sepsis-ALI. METHODS: Lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) were used to establish the cell model of sepsis-ALI in vitro. Levels of genes and proteins were measured by RT-qPCR and western blotting...

BACKGROUND: Acute lung injury (ALI) is the local inflammatory response of the lungs involved in a variety of inflammatory cells. Macrophages are immune cells and inflammatory cells widely distributed in the body. Acid-sensitive ion channel 1a (ASIC1a) is involved in the occurrence of ALI, but the mechanism is still unclear. METHODS: Kunming mouse were stimulated by Lipopolysaccharides (LPS) to establish ALI model in vivo, and RAW264.7 cells were stimulated by LPS to establish inflammatory model in vitro...

When coronavirus disease 2019 (COVID-19) develops into the severe phase, lung injury, acute respiratory distress syndrome, and/or respiratory failure could develop within a few days. As a result of pulmonary tissue injury, pathomorphological changes usually present endothelial dysfunction, inflammatory cell infiltration of the lung interstitium, defective gas exchange, and wall leakage. Consequently, COVID-19 may progress to tremendous lung injury, ongoing lung failure, and death. Exploring the treatment drugs has important implications...

Background: Critically ill patients on supplemental oxygen therapy eventually develop acute lung injury (ALI). Reactive oxygen species (ROS) produced during ALI perturbs the mitochondrial dynamics resulting in cellular damage. Genetic deletion of the mitochondrial A-kinase anchoring protein 1 (Akap1) in mice resulted in mitochondrial damage, Endoplasmic reticulum (ER) stress, increased expression of mitophagy proteins and pro-inflammatory cytokines, exacerbating hyperoxia-induced Acute Lung Injury (HALI). Objective: Despite a strong causal link between mitochondrial dysfunction and HALI, the mechanisms governing the disease progression at the transcriptome level is unknown...

Objective: Obesity-induced endoplasmic reticulum (ER) stress plays a role in increased susceptibility to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The activation of peroxisome proliferator-activated receptor- γ (PPAR γ ) is associated with lung protection and is effective in ameliorating ER stress and mitochondrial dysfunction. The aim of this study was to investigate the expression of PPAR γ in the lung tissues of obese mice and explore whether the PPAR γ -dependent pathway could mediate decreased ALI/ARDS by regulating ER stress and mitochondrial biogenesis...

Adiponectin (APN) is an adipokine concerned in the regulation of glucose metabolism, insulin sensitivity and fatty acid oxidation. APN plays a critical role in viral infections by regulating the immune response through its anti-inflammatory/pro-inflammatory axis. Reduction of APN may augment the severity of viral infections because APN inhibits immune cells' response via suppression of inflammatory signaling pathways and stimulation of adenosine monophosphate protein kinase (AMPK). Moreover, APN inhibits the stimulation of nuclear factor kappa B (NF-κB) and regulates the release of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukins (IL-18, IL-6)...

AIMS: Acute lung injury (ALI) is a life-threatening clinical problem with high mortality rate and limited treatments or preventive options that represents a major challenge for clinicians. Diacerein (DIA) is a multi-target anthraquinone derivative with potent anti-inflammatory action. The aim of this study is to assess the protective effect of DIA and its potential molecular targets against lipopolysaccharide (LPS)-induced ALI in rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were orally administrated DIA (50 mg/kg) for 5 consecutive days followed by a single intraperitoneal injection of LPS (5mg/kg)...

Pinelliae rhizoma (PR), one kind of commonly-used Chinese herbs, is generally prescribed to treat various respiratory diseases, including acute lung injury (ALI). However, the accurate bioactive ingredients of PR and the underlying pharmacological mechanism have both not been fully elucidated. Therefore, this study aimed to identify the bioactive ingredients that could alleviate lipopolysaccharide (LPS)-induced ALI and explore the possible mechanism involved. Our results confirmed that LPS infection indeed caused acute inflammatory damage in mice lung, accompanying with the enhancement of IL-1β contents and the activation of the NLRP3 inflammasome in lung tissue and macrophagocyte, all of which were remarkably ameliorated by PR treatment...

Vascular barrier dysfunction due to endothelial hyperpermeability has been associated with the pathophysiology of sepsis and severe lung injury, which may inflict acute respiratory distress syndrome (ARDS). Our group is focused on the mechanisms operating towards the regulation of endothelial permeability, to contribute in the development of efficient and targeted countermeasures against ARDS. Unfortunately, the number of ARDS-related deaths in the intensive care units has dramatically increased during the COVID-19 era...

Acute lung injury is a life-threatening medical problem induced by sepsis or endotoxins and may be associated with enhanced Endoplasmic reticulum stress (ER stress). Vitamin-D (Vit-D) possesses an anti-inflammatory effect; however, this specific mechanism on acute lung injury is still unknown. Here we scrutinize the mechanism of Vit-D on ALI models and explored the Vit-D augmented miRNA's role in regulating the ER stress pathway in ALI. Sepsis was induced by CLP, and Endotoxemia was caused by LPS. We found that Vit-D alleviates pulmonary edema, improves lung histoarchitecture, infiltration of neutrophils, endothelial barrier in mice, and improves ER stress markers ATF6 and CHOP expression elevated by CLP/LPS induce ALI...

BACKGROUND: This study explored the role and mechanism of salidroside in sepsis-associated acute lung injury (ALI). METHOD: Sepsis-associated ALI in rats was induced by cecal ligation and perforation method, while lipopolysaccharide (LPS) was used to stimulate cell model. After the treatment of salidroside and dexamethasone (DEX), hematoxylin and eosin staining was applied to evaluate the rat lung injury. Next, the number of total cells and neutrophils in rat bronchoalveolar lavage fluid (BALF) was counted, and the lung wet/dry (W/D) ratio and water content were measured...

OBJECTIVE: Apoptosis plays a major role in the progression of acute respiratory distress syndrome (ARDS) that may involve the interaction of the high mobility group box 1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). However, the underlying mechanism remains unclear. Thus, we aimed to explore the mechanisms of HMGB1-RAGE axis-induced apoptosis in ARDS. METHODS: Blood samples from ARDS patients and healthy volunteers were collected to investigate the correlation between serum HMGB1 levels and the severity of ARDS in patients...

Endotoxin-induced acute lung injury (ALI) is a challenging life-threatening disease for which no specific therapy exists. Mitochondrial dysfunction is corroborated as hallmarks in sepsis which commonly disrupt mitochondria-centered cellular communication networks, especially mitonuclear crosstalk, where the ubiquitous cofactor nicotinamide adenine dinucleotide (NAD+ ) is essential for mitonuclear communication. Heme oxygenase-1 (HO-1) is critical for maintaining mitochondrial dynamic equilibrium and regulating endoplasmic reticulum (ER) and Golgi stress to alleviating acute lung injury...

Background: Lipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities. Methods: We investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis...

BACKGROUND: The inappropriate apoptosis of macrophages plays an important role in the pathogenesis of sepsis-induced acute lung injury, however, the detailed regulatory mechanisms remain largely unknown. As an endogenous apoptosis pathway, endoplasmic reticulum (ER) stress plays an important role in cell damage in patients with sepsis. Clarifying the ER stress response and its effect on macrophages during the development of sepsis is helpful to explore new strategies for the prevention and treatment of ALI in sepsis...

OBJECTIVE: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). METHODS: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR...

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction play a pivotal role in the pathological process of sepsis-induced acute lung injury (ALI). Quercetin has been proved to exert anti-inflammation in ALI. This study aimed to explore the protection mechanism of quercetin against sepsis-induced ALI via suppressing ER stress and mitochondrial dysfunction. Cecal ligation and puncture (CLP) mouse model was established to mimic sepsis, and LPS was used to stimulate murine lung epithelial (MLE-12) cells...

The goal of this study was to analyze whether mitochondria-associated endoplasmic reticulum membrane (MAMs) dysfunction mediated arsenic (As)-evoked pulmonary ferroptosis and acute lung injury (ALI). As exposure led to alveolar structure damage, inflammatory cell infiltration and pulmonary function decline in mice. Ferritin, the marker of iron overload, was increased, GPX4, the index of lipid peroxidation, was decreased in As-exposed lungs and pulmonary epithelial cells (MLE-12). Pretreatment with ferrostatin-1 (Fer-1), the inhibitor of ferroptosis, alleviated As-evoked ALI...

Few pharmacological interventions are able to improve the mortality rate of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). The aim of this research was to elucidate whether endoplasmic reticulum (ER) stress and c‑Jun‑N‑terminal kinase (JNK)‑mitochondria pathways serve important roles in ALI/ARDS and to determine whether the key component Sab is a potential treatment target. The current study investigated the activation of ER stress and the JNK pathway, the content of JNK located on the mitochondria during ER stress and lipopolysaccharide (LPS)‑induced ALI/ARDS by western blot analysis...

Rutaecarpine (RUT) is an alkaloid isolated from Tetradium ruticarpum , which has been reported to protect against several inflammatory diseases. However, to the best of our knowledge, the role of RUT in acute lung injury (ALI) and the specific molecular mechanism remain unknown. In the present study, an in vitro model of ALI was established in BEAS-2B cells by lipopolysaccharide (LPS) administration. Cell viability following RUT treatment with or without LPS stimulation was evaluated using a Cell Counting Kit-8 assay...