Acute lung injury and endoplasmic reticulum stress

Sepsis-induced acute lung injury (ALI) is a serious complication of sepsis and the predominant cause of death. Exosomes released by lung tissue cells critically influence the progression of ALI during sepsis by modulating the inflammatory microenvironment. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbates ALI in septic infection remain undefined. Our study found increased levels of exosomal Tenascin-C (TNC) in the plasma of both patients and mice with ALI, showing a strong association with disease progression...

OBJECTIVES: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). METHODS: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines...

Nanoplastics are widely distributed in indoor and outdoor air and can be easily inhaled into human lungs. However, limited studies have investigated the impact of nanoplastics on inhalation toxicities, especially on the initiation and progression of chronic obstructive pulmonary disease (COPD). To fill the gap, the present study used oronasal aspiration to develop mice models. Mice were exposed to polystyrene nanoplastics (PS-NPs) at three concentrations, as well as the corresponding controls, for acute, subacute, and subchronic exposure...

INTRODUCTION: Various immune cell types play critical roles in sepsis with numerous distinct subsets exhibiting unique phenotypes even within the same cell population. Single-cell RNA sequencing (scRNA-seq) enables comprehensive transcriptome profiling and unbiased cell classification. In this study, we have unveiled the transcriptomic landscape of immune cells in sepsis through scRNA-seq analysis. METHODS: We induced sepsis in mice by cecal ligation and puncture...

Acute lung injury (ALI) is a life-threatening clinical disorder with high mortality rate. Ferroptosis is a new type of programmed cell death with lipid peroxidation and iron ion overloading as the main characteristics. Endoplasmic reticulum (ER) stress and ferroptosis play pivotal roles in the pathogenesis of ALI. The study aimed to investigate the underlying relationship between ER stress and ferroptosis in ALI. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated LPS-induced inflammation, and decreased IL-1β, IL-6, and TNF-α levels in BALF and lungs...

Lipid membranes and lipid-rich organelles are targets of peroxynitrite (ONOO- ), a highly reactive species generated under nitrative stress. We report a membrane-localized phospholipid ( DPPC-TC-ONOO - ) that allows the detection of ONOO- in diverse lipid environments: biomimetic vesicles, mammalian cell compartments, and within the lung lining. DPPC-TC-ONOO - and POPC self-assemble to membrane vesicles that fluorogenically and selectively respond to ONOO- . DPPC-TC-ONOO - , delivered through lipid nanoparticles, allowed for ONOO- detection in the endoplasmic reticulum upon cytokine-induced nitrative stress in live mammalian cells...

BACKGROUND: The cellular endoplasmic reticulum (ER) is responsible for various functions, including protein synthesis, folding, distribution, and calcium ion storage. Studies have linked ER stress with acute lung injury (ALI), which can result in oxidative stress and even cell death. Peroxynitrite (ONOO- ) is a well-known reactive oxygen species (ROS) that contributes to various physiological and pathological processes in oxidative stress diseases. To understand the role of ER ONOO- in ALI, it is crucial to accurately measure its level in the ER...

Transmembrane protein 16A (TMEM16A) is one of the members of the ten-member family of "transmembrane protein 16", playing critical roles in infection and solid organ injury. Acute lung injury (ALI) is a devastating disease which could be triggered by sepsis, trauma, and ischemia reperfusion. However, molecular mechanisms contributing to ALI are poorly understood at presently. In this study, we investigated the role of TMEM16A in sepsis-induced ALI using TMEM16A-deficient mice. Sepsis-induced ALI model was established by intratracheal injection of lipopolysaccharide (LPS)...

BACKGROUND: Acute lung injury (ALI), along with the more severe condition--acute respiratory distress syndrome (ARDS), is a major cause of respiratory failure in critically ill patients with high morbidity and mortality. Inositol-requiring protein 1α (IRE1α)/X box protein-1 (XBP1) pathway was proved to regulate lipopolysaccharide (LPS)-induced lung injury and inflammation. Yet, its role on epithelial β-catenin in LPS-induced ALI remains to be elucidated. METHODS: LPS-induced models were generated in mice (5 mg/kg) and Beas-2B cells (200 μg/mL)...

BACKGROUND: Activating transcription factor 3 (ATF3) is a nuclear protein that is widely expressed in a variety of cells. It is a stress-inducible transcription gene and a member of the activating transcription factor/cAMP responsive element-binding protein (ATF/CREB) family. METHODS: The comprehensive literature review was conducted by searching PubMed and Google Scholar. Search terms used were "ATF3", "ATF3 and (ALI or ARDS)", "ATF3 and COPD", "ATF3 and PF", and "ATF3 and Posttranslational modifications"...

Perioperative hyperoxia therapy is of great significance to save the lives of patients, but little is known about the possible mechanisms that induce hyperoxia-induced acute lung injury (HALI) and the measures for clinical prevention and treatment. In this experiment, the models were established with a feeding chamber with automatic regulation of oxygen concentration. The results showed that with the increase in inhaled oxygen concentration and the prolongation of exposure time, the severity of lung injury also increases significantly, reaching the diagnostic indication of HALI after 48 h of inhaling 95 % oxygen concentration...

Acute lung injury (ALI) is a common inflammatory respiratory disorder characterized by a high incidence and mortality rate. This study aimed to investigate the potential therapeutic effects of the neutrophil elastase inhibitor Sivelestat sodium (SIV) in improving endoplasmic reticulum stress (ERS) while treating lipopolysaccharide (LPS)-induced ALI. An ALI model was established using LPS induction. The effects of SIV on ALI were observed both in vivo and in vitro, along with its impact on ERS. Lung tissue damage was assessed using Hematoxylin-eosin (H&E) staining...

BACKGROUND: Critical illness is hallmarked by severe stress and organ damage. Fibroblast growth factor 21 (FGF21) has been shown to rise during critical illness. FGF21 is a pleiotropic hormone that mediates adaptive responses to tissue injury and repair in various chronic pathological conditions. Animal studies have suggested that the critical illness-induced rise in FGF21 may to a certain extent protect against acute lung, liver, kidney and brain injury. However, FGF21 has also been shown to mediate fasting-induced loss of muscle mass and force...

Acute pancreatitis (AP) may be associated with both local and systemic complications. Although it is usually self-limiting, up to 20% of patients develop severe acute pancreatitis (SAP), which leads to systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction and failure affecting the lung, kidney, liver and heart. Patients who survive the condition frequently develop devastating long-term consequences such as diabetes mellitus, exocrine pancreatic insufficiency, chronic pancreatitis (CP) and poor quality of life...

INTRODUCTION: Acute lung injury (ALI) attracted attention among physicians because of its high mortality. We aimed to determine whether the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway is involved in the protective effects of penehyclidine hydrochloride (PHC) against lipopolysaccharide (LPS)-induced ALI. METHODS: H&E staining was used to observed pathological changes in the lung tissues. ELISA was used to evaluate the concentration of inflammatory mediators in the bronchoalveolar lavage fluid (BALF)...

Barrier dysfunction is the hallmark of severe lung injury, including acute respiratory distress syndrome. Efficient medical countermeasures to counteract endothelial hyperpermeability do not exist, hence the mortality rates of disorders related to barrier abnormalities are unacceptable high. The unfolded protein response is a highly conserved mechanism, which aims to support the cells against endoplasmic reticulum stress, and ATF6 is a protein sensor that triggers its activation. In the current study, we investigate the effects of ATF6 suppression in LPS-induced endothelial inflammation...

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), the prime causes of morbidity and mortality in critically ill patients, are usually treated by general supportive treatments. Endoplasmic reticulum autophagy (ER-phagy) maintains cellular homeostasis by degrading damaged endoplasmic reticulum (ER) fragments and misfolded proteins. ER-phagy is crucial for maintaining ER homeostasis and improving the internal environment. ER-phagy has a particular role in some aspects, such as immunity, inflammation, cell death, pathogen infection, and collagen quality...

Cholesterol-25-hydroxylase (CH25H), the biosynthetic enzyme for 25-hydroxycholesterol (25HC), is most highly expressed in the lung, but its role in lung biology is poorly defined. Recently, we reported that Ch25h is induced in monocyte-derived macrophages recruited to the airspace during resolution of lung inflammation and that 25HC promotes Liver X Receptor (LXR)-dependent clearance of apoptotic neutrophils by these cells. Ch25h and 25HC are, however, also robustly induced by lung-resident cells during the early hours of lung inflammation, suggesting additional cellular sources and targets...

Ferroptosis plays a critical role in LPS-induced acute lung injury and is modulated by endoplasmic reticulum stress (ERS). As a typical ER stress-responsive protein, recently mesencephalic astrocyte-derived neurotrophic factor (MANF) has been demonstrated to attenuate LPS-induced acute lung injury (ALI) through repressing macrophage activation. However, whether MANF exerts a preventive role on ferroptosis and excess ER stress remains unclear. Here, we first built a protein-protein interaction (PPI) network to obtain potential interacting proteins related to MANF through STRING and GeneMANIA...

We investigated the effects and underlying mechanisms of activated leukocyte adhesion molecule (ALCAM) on acute lung injury (ALI) by using lipopolysaccharide (LPS)-induced ALI animal model and LPS-induced inflammation in vitro. In LPS-stimulated mice, ALCAM deficiency relieved lung injury, which manifested as reduced pathological changes in the lung tissue, reduced pulmonary edema, and reduced vascular permeability. Furthermore, we demonstrated that ALCAM deficiency reduced the infiltration of inflammatory cells, including neutrophil, eosinophil, and macrophages; the release of inflammatory cytokines, including IL-1β, IL-6, TNF-α, and COX2; and reduced the protein level of TLR4/NF-κB pathway (TLR4, MyD88, p-IkBɑ, and p-NF-κB p65)...