Ficolin B secreted by alveolar macrophage exosomes exacerbates bleomycin-induced lung injury via ferroptosis through the cGAS-STING signaling pathway

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(8)

Published: Aug. 30, 2023

Pathogenesis exploration and timely intervention of lung injury is quite necessary as it has harmed human health worldwide for years. Ficolin B (Fcn B) a recognition molecule that can recognize variety ligands play an important role in mediating the cell cycle, immune response, tissue homeostasis lung. However, Fcn bleomycin (BLM)-induced obscure. This study aims to investigate sources its mechanism BLM-induced injury. WT, Fcna-/-, Fcnb-/- mice were selected construct model. Lung epithelial cells utilized Exosomes secreted from alveolar macrophages (AMs) applied by transporting B. Clinical data suggested M-ficolin (homologous was raised plasma interstitial disease (ILD) patients. In mouse model, macrophage-derived aggravated fibrosis. further promoted development autophagy ferroptosis. Remarkably, experiment results revealed transported AMs exosomes accelerated ferroptosis through activation cGAS-STING pathway. contrast, application 3-Methyladenine (3-MA) reversed promotion effect on damage inhibiting autophagy-dependent Meanwhile, facilitated fibrosis via summary, this demonstrated exacerbated promoting signaling

Language: Английский

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Neutrophil extracellular traps contribute to immunothrombosis formation via the STING pathway in sepsis-associated lung injury

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 25, 2023

Neutrophil extracellular traps (NETs) are involved in the activation and dysfunction of multiple overlapping interacting pathways, including immune response to injury, inflammation, coagulation, which contribute pathogenesis sepsis-induced acute lung injury (SI-ALI). However, how NETs mediate relationship between inflammation coagulation has not been fully clarified. Here, we found that NETs, through stimulator interferon genes (STING) activation, induced endothelial cell damage with abundant production tissue factor (TF), magnified dysregulation inflammatory coagulant responses resulted poor prognosis SI-ALI model mice. Disruption inhibition STING improved outcomes septic mice reduced coagulation. Furthermore, Toll-like receptor 2 (TLR2) on surface cells was interaction pathway. Collectively, these findings demonstrate activate cascade a STING-dependent manner development SI-ALI.

Language: Английский

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Perillaldehyde ameliorates lipopolysaccharide-induced acute lung injury via suppressing the cGAS/STING signaling pathway

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 130, P. 111641 - 111641

Published: Feb. 18, 2024

Language: Английский

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Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(8), P. 1660 - 1672

Published: April 8, 2024

Language: Английский

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cGAS-STING targeting offers therapy choice in lung diseases

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 7, 2025

Cyclic GMP/AMP (cGAMP) synthase (cGAS), along with the endoplasmic reticulum (ER)-associated stimulator of interferon genes (STING), are crucial elements type 1 response. cGAS senses microbial DNA and self-DNA, labeling cGAS-STING as a mechanism in autoimmunity, sterile inflammatory responses, cellular senescence. However, chronic aberrant activation axis results autoimmune diseases. has emerged vital driving inflammation-related diseases, including lung Insights into biology pathway have enabled discovery small-molecule agents which potential to inhibit In this review, we first outline principal components signaling cascade. Then, discuss recent research that highlights general mechanisms by contributes focus on summarizing list bioactive compounds pathway, reviewing their mechanisms.These review novel groundbreaking therapeutic possibilities through targeting

Language: Английский

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Genetically Engineered Cellular Nanovesicle as Targeted DNase I Delivery System for the Clearance of Neutrophil Extracellular Traps in Acute Lung Injury

Advanced Science, Journal Year: 2023, Volume and Issue: 10(32)

Published: Sept. 27, 2023

Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are prevalent critical illnesses with a high mortality rate among patients in intensive care units. Neutrophil extracellular traps (NETs) implicated the pathogenesis of ALI/ARDS and represent promising therapeutic target. However, clinical application deoxyribonuclease I (DNase I), only drug currently available to clear NETs, is limited due lack precise efficient delivery strategies. Therefore, targeted DNase inflamed remains issue be addressed. Herein, novel biomimetic system developed (DCNV) that employs genetically bioorthogonally engineered cellular nanovesicles for pulmonary NETs clearance. The CXC motif chemokine receptor 2 overexpressed can mimic inflammatory chemotaxis neutrophils ALI/ARDS, leading enhanced accumulation. Furthermore, immobilized through bioorthogonal chemistry exhibits remarkable enzymatic activity degradation, thus restraining inflammation safeguarding tissue lipopolysaccharide‐induced ALI murine model. Collectively, findings present groundbreaking proof‐of‐concept utilization deliver treating ALI/ARDS. This innovative strategy may usher new era development pharmacological interventions various inflammation‐related diseases.

Language: Английский

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The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 8, 2024

The cyclic guanosine monophosphate (GMP)-adenosine (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component the innate immune system, is involved in development several diseases. Ectopic DNA-induced inflammatory responses are pathological processes. Repeated damage to tissues and metabolic organelles releases a large number damage-associated molecular patterns (mitochondrial DNA, nuclear exogenous DNA). DNA fragments released into cytoplasm sensed by sensor cGAS initiate through bridging protein STING. Many recent studies have revealed regulatory role cGAS-STING pathway cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting can significantly inhibit hypertrophy cell infiltration. Therefore, this review intended identify risk factors for activating reduce risks simultaneously further elucidate biological function field, well its potential therapeutic target.

Language: Английский

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Neutrophil extracellular traps and their implications in airway inflammatory diseases

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 10

Published: Jan. 12, 2024

Neutrophil extracellular traps (NETs) are essential for immune defense and have been increasingly recognized their role in infection inflammation. In the context of airway inflammatory diseases, there is growing evidence suggesting involvement significance NETs. This review aims to provide an overview formation mechanisms components NETs impact on various including acute lung injury/ARDS, asthma, chronic obstructive pulmonary disease (COPD) cystic fibrosis. By understanding inflammation, we can gain valuable insights into underlying pathogenesis these diseases identify potential targets future therapeutic strategies that either target or modulate harmful effects. Further research warranted elucidate complex interactions between inflammation develop targeted therapies effectively mitigate detrimental effects while preserving beneficial functions host defense.

Language: Английский

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Icariside II alleviates lipopolysaccharide-induced acute lung injury by inhibiting lung epithelial inflammatory and immune responses mediated by neutrophil extracellular traps

Life Sciences, Journal Year: 2024, Volume and Issue: 346, P. 122648 - 122648

Published: April 15, 2024

Acute lung injury (ALI) is a life-threatening disease characterized by inflammatory cell infiltration and epithelial injury. Icariside II (ICS II), one of the main active ingredients Herba Epimedii, exhibits anti-inflammatory immunomodulatory effects. However, effect mechanism ICS in ALI remain unclear. The purpose current study was to investigate pharmacological underlying ALI. Models neutrophil-like cells, human peripheral blood neutrophils, lipopolysaccharide (LPS)-induced mouse model were utilized. RT-qPCR Western blotting determined gene protein expression levels. Protein distribution quantification analyzed immunofluorescence. significantly reduced histopathological damage, edema, infiltration, it pro-inflammatory cytokines There an excessive activation neutrophils leading significant production NETs mice, process mitigated administration II. In vivo vitro studies found that could decrease NET formation targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed reduces overproduction dsDNA, NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway mediators release cells. This suggested may alleviate LPS-induced modulating response, indicating its potential as therapeutic agent for treatment.

Language: Английский

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Therapeutic efficacy of thrombin-preconditioned mesenchymal stromal cell-derived extracellular vesicles on Escherichia coli-induced acute lung injury in mice

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 7, 2024

Acute lung injury (ALI) following pneumonia involves uncontrolled inflammation and tissue injury, leading to high mortality. We previously confirmed the significantly increased cargo content extracellular vesicle (EV) production in thrombin-preconditioned human mesenchymal stromal cells (thMSCs) compared those naïve other preconditioning methods. This study aimed investigate therapeutic efficacy of EVs derived from thMSCs protecting against an Escherichia coli (E. coli)-induced ALI mouse model. In vitro, RAW 264.7 were stimulated with 0.1 µg/mL liposaccharides (LPS) for 1 h, then treated either PBS (LPS Ctrl) or 5 × 107 particles thMSC-EVs + thMSC-EVs) 24 h. Cells media harvested flow cytometry ELISA. vivo, ICR mice anesthetized, intubated, administered 2 CFU/100 µl E. coli. 50 min after, µL saline (ECS) 109 particles/50 (EME). Three days later, was assessed using extracted tissue, bronchoalveolar lavage fluid (BALF), vivo computed tomography scans. One-way analysis variance post-hoc TUKEY test used compare experimental groups statistically. IL-1β, CCL-2, MMP-9 levels lower LPS group than Ctrl group. The percentages M1 macrophages normal control, Ctrl, thMSC-EV 12.5, 98.4, 65.9%, respectively. EME exhibited histological scores alveolar congestion, hemorrhage, wall thickening, leukocyte infiltration ECS wet-dry ratio lungs BALF CCL2, TNF-a, IL-6 CT revealed a percentage damaged Intratracheal administration reduced coli-induced damage. Overall, these results suggest therapeutically enhanced as novel promising option ARDS/ALI.

Language: Английский

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