Pyroptosis in health and disease: mechanisms, regulation and clinical perspective

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

---

CMPK2 promotes NLRP3 inflammasome activation via mtDNA‐STING pathway in house dust mite‐induced allergic rhinitis

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background House dust mite (HDM) is the leading allergen for allergic rhinitis (AR). Although sensitisation by inhaled allergens renders susceptible individuals prone to developing AR, molecular mechanisms driving this process remain incompletely elucidated. Objective This study aimed elucidate underlying HDM‐induced AR. Methods We examined expression of cytidine/uridine monophosphate kinase 2 (CMPK2), STING and NLRP3 inflammasome in both AR patients mice. Additionally, we investigated role CMPK2 activation Results The CMPK2, was significantly increased nasal mucosa compared non‐AR controls. A positive correlation found between levels STING, NLRP3, ASC, CASP1 IL‐1β. HDM treatment up‐regulated overexpression enhanced human epithelial cells (HNEPCs). mitochondrial reactive oxygen species (mtROS) production following exposure contributed dysfunction release DNA (mtDNA), which activated cyclic GMP‐AMP synthase (cGAS)‐STING pathway. Remarkably, depletion mtDNA or inhibition signalling reduced HNEPCs. In vivo, genetic knockout alleviated ameliorated clinical symptoms Conclusions Our results suggest that promotes through up‐regulation ensuing mtDNA‐STING pathway, hence revealing additional therapeutic target Key points Cytidine/uridine (CMPK2) mice with caused via (mtDNA)‐STING Blocking house (HDM)‐challenged

Language: Английский

---

Pharmacological inhibition of cGAS ameliorates postoperative cognitive dysfunction by suppressing caspase-3/GSDME-dependent pyroptosis

Neurochemistry International, Journal Year: 2024, Volume and Issue: 178, P. 105788 - 105788

Published: June 5, 2024

Language: Английский

---

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

---

Novel insight into cGAS-STING pathway in ischemic stroke: from pre- to post-disease

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 17, 2023

Ischemic stroke, a primary cause of disability and the second leading mortality, has emerged as an urgent public health issue. Growing evidence suggests that Cyclic GMP-AMP synthase (cGAS)- Stimulator interferon genes (STING) pathway, component innate immunity, is closely associated with microglia activation, neuroinflammation, regulated cell death in ischemic stroke. However, mechanisms underlying this pathway remain inadequately understood. This article comprehensively reviews existing literature on cGAS-STING its multifaceted relationship Initially, it examines how various risk factors pre-disease such metabolic dysfunction senescence (e.g., hypertension, hyperglycemia, hyperlipidemia) affect relation to Subsequently, we explore depth potential pathophysiological between oxidative stress, endoplasmic reticulum neuroinflammation well including ferroptosis PANoptosis following cerebral ischemia injury. Finally, intervention targeting may serve promising therapeutic strategies for addressing Taken together, review concludes shed light exploration new against

Language: Английский

---

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

---

Saikosaponin d protects pancreatic acinar cells against cerulein‐induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS‐STING pathway

Journal of Applied Toxicology, Journal Year: 2024, Volume and Issue: 44(7), P. 1005 - 1013

Published: March 11, 2024

Abstract Acute pancreatitis represents an inflammatory disease featuring pancreatic necrosis and inflammation. Inflammatory injury of acinar cells (PACs) is critically involved in the initiation progression acute pancreatitis. Pyroptosis, a new kind programmed cell death concomitant with low‐grade reaction, plays function pathology. It unclear whether saikosaponin d (SSd), pharmacologically active natural product, could protect PACs by regulating pyroptosis. Here, we established PAC model vitro using cerulein to treat AR42J cells. SSd restored viability proliferation lowered release enzymes interleukins cerulein‐treated Cerulein‐induced pyroptosis was evidenced typical ultrastructural changes NLRP3/caspase‐1 activation cells, but attenuated cerulein‐induced inhibited pathway. Mechanically, reduced mitochondrial damage mtDNA release, blocked cGAS‐STING signaling treated cerulein, contributing inhibition NLRP3‐mediated Furthermore, abolished cerulein‐elevated oxidative stress leading mitigation In conclusion, protected against alleviating inhibiting pathway, it be therapeutic candidate for

Language: Английский

---

Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 13, 2025

Language: Английский

---

Mitochondrial DNA in atherosclerosis research progress: a mini review

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 7, 2025

Atherosclerosis (AS) is a chronic inflammatory disease that primarily affects large and medium-sized arteries one of the leading causes death worldwide. This article reviews multifaceted role mitochondrial DNA (mtDNA) in AS, including its structure, function, release, relationship with inflammation. Damage release mtDNA are considered central drivers development as they participate progression AS by activating pathways affecting lipid metabolism. Therefore, therapeutic strategies targeting downstream effects may provide new avenues to address this global health challenge.

Language: Английский

---

Neutrophil Extracellular Traps in Atherosclerosis: Research Progress

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2336 - 2336

Published: March 6, 2025

Atherosclerosis (AS) is a disease characterised by the accumulation of atherosclerotic plaques on inner walls blood vessels, resulting in their narrowing. In its early stages, atherosclerosis remains asymptomatic and undetectable conventional pathological methods. However, as progresses, it can lead to series cardiovascular diseases, which are leading cause mortality among middle-aged elderly populations worldwide. Neutrophil extracellular traps (NETs) composed chromatin granular proteins released neutrophils. Upon activation external stimuli, neutrophils undergo reactions, release NETs subsequent cell death, process termed NETosis. Research has demonstrated that NETosis means contribute immune responses. studies neutrophil have identified primary various inflammation-induced including cystic fibrosis, systemic lupus erythematosus, rheumatoid arthritis. Consequently, present review will concentrate impact formation, analysing from molecular biology perspective. This involve systematic dissection proteomic components signal pathways.

Language: Английский

---