Comprehending toll-like receptors: pivotal element in the pathogenesis of sepsis and its complications DOI Creative Commons
Wei Wang,

Shengtian Mu,

Dongli Yan

et al.

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

Published: May 2, 2025

Sepsis, a critical systemic inflammatory response syndrome elicited by pathogenic microorganisms, poses significant challenge in clinical practice due to its rapid progression and potential for multi-organ failure. This review delineates the intricate roles of Toll-like receptors (TLRs), essential components innate immune system, mediating host responses during sepsis. TLRs recognize pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs), thereby initiating signaling cascades that lead synthesis pro-inflammatory cytokines chemokines. However, dysregulation TLR can precipitate hyper-inflammatory state known as “cytokine storm,” characterized excessive tissue damage complications such Acute Respiratory Distress Syndrome (ARDS) acute kidney injury (AKI). Several therapeutic strategies targeting pathways are under exploration mitigate adverse effects Despite advancements, gaps remain, including need robust validation understanding expression variability among individuals. Future research should focus on elucidating precise mechanisms governing TLR-mediated developing human-specific interventions. aims consolidate current knowledge sepsis, highlighting their dual both defenders against infection contributors pathological conditions, informing future strategies.

Language: Английский

Extracellular vesicle-packaged GBP2 from macrophages aggravates sepsis-induced acute lung injury by promoting ferroptosis in pulmonary vascular endothelial cells DOI Creative Commons
Zhixi Li,

Yue Bu,

Cheng Wang

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103614 - 103614

Published: March 1, 2025

Macrophages play a critical role in the development of sepsis-induced acute lung injury (si-ALI), with extracellular vesicles (EVs) acting as crucial mediators. However, effects and mechanisms macrophage-derived EVs on si-ALI remain unclear. This study demonstrated that induce endothelial ferroptosis barrier disruption during sepsis. Through proteomic sequencing reanalysis transcriptomic single-cell data, guanylate-binding protein 2 (GBP2) was identified key EV molecule. Elevated GBP2 expression observed monocytes from peripheral blood sepsis patients, LPS-stimulated THP-1 RAW264.7 cells their secreted EVs, macrophages within lungs CLP mice. Additionally, showed positive correlation vascular biomarkers, including ANGPT2, Syndecan-1, sTM. Modulating levels affected EV-induced cells. The mechanism by which binds directly to OTUD5 promotes GPX4 ubiquitination elucidated using RNA interference, adeno-associated virus transfection, endothelial-specific Gpx4 knockout A high-throughput screening small-molecule compounds targeting conducted. Molecular docking, molecular dynamics simulations, cellular thermal shift assays further confirmed Plantainoside D (PD) has potent binding affinity for GBP2. PD treatment inhibited interaction between OTUD5, leading reduction ubiquitination. Further research revealed enhanced pulmonary protective inhibition. In conclusion, this explored EV-mediated signaling si-ALI, highlighting GBP2-OTUD5-GPX4 axis driver injury. Targeting presents potential therapeutic strategy si-ALI.

Language: Английский

Citations

0
Wogonin attenuates septic cardiomyopathy by suppressing ALOX15-mediated ferroptosis DOI
Ye Hua, Lin Wu, Yanmei Liu

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Language: Английский

Citations

0
Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1 DOI
Hongwei Zhao, Haiyan Zhang, Jian‐Yu Shi

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119649 - 119649

Published: April 1, 2025

Language: Английский

Citations

0
Ferroptosis targeting offers a Therapeutic Target for Septic cardiomyopathy DOI
Ping Zhou, Mengxue Liu, Tao Lv

et al.

Tissue and Cell, Journal Year: 2025, Volume and Issue: 95, P. 102930 - 102930

Published: April 25, 2025

Language: Английский

Citations

0
Comprehending toll-like receptors: pivotal element in the pathogenesis of sepsis and its complications DOI Creative Commons
Wei Wang,

Shengtian Mu,

Dongli Yan

et al.

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

Published: May 2, 2025

Sepsis, a critical systemic inflammatory response syndrome elicited by pathogenic microorganisms, poses significant challenge in clinical practice due to its rapid progression and potential for multi-organ failure. This review delineates the intricate roles of Toll-like receptors (TLRs), essential components innate immune system, mediating host responses during sepsis. TLRs recognize pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs), thereby initiating signaling cascades that lead synthesis pro-inflammatory cytokines chemokines. However, dysregulation TLR can precipitate hyper-inflammatory state known as “cytokine storm,” characterized excessive tissue damage complications such Acute Respiratory Distress Syndrome (ARDS) acute kidney injury (AKI). Several therapeutic strategies targeting pathways are under exploration mitigate adverse effects Despite advancements, gaps remain, including need robust validation understanding expression variability among individuals. Future research should focus on elucidating precise mechanisms governing TLR-mediated developing human-specific interventions. aims consolidate current knowledge sepsis, highlighting their dual both defenders against infection contributors pathological conditions, informing future strategies.

Language: Английский

Citations

0