Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis DOI Creative Commons

Peizhi Tao,

Beiting Su,

Xueyan Mao

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103594 - 103594

Published: March 13, 2025

Cigarette smoke (CS) exposure amplifies neutrophil accumulation. IL-35, a novel cytokine with anti-inflammatory properties, is involved in protection against asthma. However, the biological roles of neutrophils and precise molecular mechanisms IL-35 CS exposed-asthma remain unclear. We showed that exacerbation leads to dramatically increased counts an imbalance DC-Th17/Treg immune responses. RNA sequencing revealed NETs, part key process neutrophils, were significantly upregulated context treatment downregulated NET-associated gene expression. Targeted degradation rather than depletion, alleviated exposed-asthma. Mechanistically, STAT3 phosphorylation promoted ferroptosis, exacerbating NET release, which turn enhanced dendritic cell (DC) antigen presentation, activated T cells, specifically Th17 differentiation while inhibiting Treg cells. acting on gp130 receptor STAT3-mediated ferroptosis-associated formation. In summary, our study mechanism by inhibited formation, subsequently alleviating neutrophilic inflammation restoring exposed-asthma, highlighting potential as targeted therapeutic strategy.

Language: Английский

ATG16L1 restrains macrophage NLRP3 activation and alveolar epithelial cell injury during septic lung injury DOI Creative Commons

Yan Bai,

Xinyu Zhan,

Qing Zhu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(4)

Published: April 1, 2025

Language: Английский

Citations

0
Lactate-induced macrophage HMGB1 lactylation promotes neutrophil extracellular trap formation in sepsis-associated acute kidney injury DOI Creative Commons
Siwei Wei, Zili Dai, Lei Wu

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: April 30, 2025

Neutrophils play a key role in sepsis-associated acute kidney injury (SAKI), common and life-threatening complication of organ failure. High mobility group box 1 (HMGB1) modulates inflammatory responses the formation neutrophil extracellular traps (NETs). The present work aimed to explore whether HMGB1 lactylation promotes NET exacerbates SAKI. Venous blood samples were collected from healthy volunteers SAKI patients. A mouse model was established using cecal ligation puncture method. coculture system macrophage-derived exosomes neutrophils established. Macrophage-derived isolated identified. ELISAs, immunofluorescence staining, coimmunoprecipitation, Western blotting utilized determine protein levels. Elevated lactate levels associated with increased patients In models, expression, promoted formation, exacerbated Lactate stimulated M1 macrophages secrete exosomes, leading accumulation release cytoplasm. Additionally, macrophages, triggering mitochondrial DNA activating cyclic GMP‒AMP synthase/stimulator interferon genes pathway. This study revealed that lactate-induced plays promoting through cGAS/STING These findings suggest could be potential target for therapeutic intervention

Language: Английский

Citations

0
Rutin ameliorates LPS-induced acute lung injury in mice by inhibiting the cGAS-STING-NLRP3 signaling pathway DOI Creative Commons
Xin Zhou, Zhibin Wang,

Yuting Wang

et al.

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

Published: May 8, 2025

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), represent critical failures with high mortality rates limited treatment options. While the flavonoid rutin exhibits documented anti-inflammatory antioxidant properties, therapeutic mechanisms in ALI/ARDS remain unclear. This study investigated rutin's efficacy against lipopolysaccharide (LPS)-induced ALI mice, a mechanistic focus on cGAS-STING pathway NLRP3 inflammasome activation. Male C57BL/6 mice were divided into Vehicle control, LPS induction, + co-treatment, Rutin monotherapy groups. was induced by intratracheal challenge, administered via gavage. Proteomics analysis, histological evaluation, immunohistochemistry, TUNEL staining, immunofluorescence, RT-qPCR, western blot, ELISA, oxidative stress assays performed to assess effects of ARDS. The proteomic profiling tissues from LPS-challenged identified significant dysregulation proteins integral cascade pyroptotic processes. Gene ontology KEGG analyses underscored pivotal role immune inflammatory responses ALI, particularly cytosolic DNA-sensing NOD-like receptor signaling pathways. administration significantly alleviated LPS-induced injury, reducing stress, apoptosis, proinflammatory cytokine levels (IL-6, IL-1β, TNF-α). Mechanistically, demonstrated dual suppression: 1) inhibiting activation through decreased expression cGAS, STING, phosphorylation TBK1/IRF3 (P<0.05), 2) attenuating NLRP3-mediated pyroptosis downregulation NLRP3-ASC-caspase1-GSDMD (P<0.05). Pharmacological STING inhibition (C-176) validated cGAS-STING-NLRP3 regulatory hierarchy pathogenesis. These findings elucidate novel mechanism coordinated suppression axis, positioning it as promising candidate for intervention.

Language: Английский

Citations

0
IDH1/MDH1 deacetylation activates the cGAS-STING pathway by promoting NETosis in acute liver failure DOI
Yukun Wang, Jin Guo, Danmei Zhang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 158, P. 114884 - 114884

Published: May 18, 2025

Language: Английский

Citations

0
Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis DOI Creative Commons

Peizhi Tao,

Beiting Su,

Xueyan Mao

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103594 - 103594

Published: March 13, 2025

Cigarette smoke (CS) exposure amplifies neutrophil accumulation. IL-35, a novel cytokine with anti-inflammatory properties, is involved in protection against asthma. However, the biological roles of neutrophils and precise molecular mechanisms IL-35 CS exposed-asthma remain unclear. We showed that exacerbation leads to dramatically increased counts an imbalance DC-Th17/Treg immune responses. RNA sequencing revealed NETs, part key process neutrophils, were significantly upregulated context treatment downregulated NET-associated gene expression. Targeted degradation rather than depletion, alleviated exposed-asthma. Mechanistically, STAT3 phosphorylation promoted ferroptosis, exacerbating NET release, which turn enhanced dendritic cell (DC) antigen presentation, activated T cells, specifically Th17 differentiation while inhibiting Treg cells. acting on gp130 receptor STAT3-mediated ferroptosis-associated formation. In summary, our study mechanism by inhibited formation, subsequently alleviating neutrophilic inflammation restoring exposed-asthma, highlighting potential as targeted therapeutic strategy.

Language: Английский

Citations

0