Inhibition of IRE1α/XBP1 axis alleviates LPS-induced acute lung injury by suppressing TXNIP/NLRP3 inflammasome activation and ERK/p65 signaling pathway DOI Creative Commons
Sijiao Wang, Lijuan Hu, Yi‐Peng Fu

et al.

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

Published: Nov. 27, 2024

Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) is a devastating clinical with high incidence and mortality rates. IRE1α-XBP1 pathway one of the three major signaling axes endoplasmic reticulum stress that involved in inflammation, metabolism, immunity. The role potential mechanisms axis ALI/ARDS has not well understood. ALI murine model was established by intratracheal administration lipopolysaccharide (LPS). Hematoxylin eosin (H&E) staining analysis bronchoalveolar lavage fluid (BALF) were used to evaluate degree injury. Inflammatory responses assessed ELISA RT-PCR. Apoptosis evaluated using TUNEL western blot. Moreover, blot, immunohistochemistry, immunofluorescence applied test expression IRE1α, XBP1, NLRP3, TXNIP, IL-1β, ERK1/2 NF-κB p65. IRE1α significantly increased after 24 h LPS treatment. Inhibition 4µ8C notably improved LPS-induced inflammatory infiltration, reduced levels IL-6, TNF-α, decreased cell apoptosis as activation NLRP3 inflammasome. Besides, LPS-stimulated Beas-2B cells, both knockdown XBP1 diminished mRNA IL-6 IL-1B, inhibited protein secreted IL-1β. Mechanically, phosphorylation nuclear translocation p65 suppressed knockdown. In summary, our findings suggest crucial pathogenesis ALI/ARDS, whose suppression could mitigate pulmonary response through TXNIP/NLRP3 inflammasome ERK/p65 pathway. Our study may provide new evidence be promising therapeutic target for ALI/ARDS.

Language: Английский

NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention DOI Creative Commons

Ping Ding,

Yuanming Song,

Yang Yang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 leads to production pro-inflammatory cellular contents, such as interleukin (IL)-1β IL-18, induction inflammatory cell death known pyroptosis, thereby amplifying or sustaining inflammation. While balanced response beneficial for resolving damage promoting tissue healing, excessive activation pyroptosis can have harmful effects. The involvement has been observed various cardiovascular diseases (CVD). Indeed, its associated are closely linked key risk factors including hyperlipidemia, diabetes, hypertension, obesity, hyperhomocysteinemia. Exercise compared with medicine highly effective measure both preventing treating CVD. Interestingly, emerging evidence suggests exercise improves CVD inhibits activity pyroptosis. In this review, mechanisms pathogenic critically discussed. Importantly, purpose emphasize managing by suppressing proposes it foundation developing novel treatment strategies.

Language: Английский

Citations

5
Kaempferol-3-O-rutinoside protects myocardial cell injury by inhibiting the TXNIP/NLRP3 pathway DOI Creative Commons
Lingli Shi,

Xiao-ni Zhao,

Juan Bai

et al.

Italian Journal of Food Science, Journal Year: 2024, Volume and Issue: 36(3), P. 291 - 300

Published: Aug. 13, 2024

Kaempferol-3-O-rutinoside (KR), a compound commonly found in green tea, has demonstrated significant myocardial protective effects. The aim of this study was to reveal the cardioprotective mechanism KR. In study, molecular docking employed predict binding affinity KR thioredoxin-interacting protein (TXNIP). An injury model H9c2 cells established using lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Lactate dehydrogenase (LDH) levels were measured specific kits, while total superoxide dismutase (T-SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) activities assessed with colorimetric assays. reactive oxygen species (ROS) level determined DCFH-DA fluorescent probe assay. addition, expression TXNIP, NLR-family pyrin domain-containing 3 (NLRP3), cysteinyl aspartate proteinase-1 (Caspase-1), thioredoxin (TRX) quantified by reverse transcription polymerase chain reaction (RT-PCR) Western blot (WB) Levels interleukin-1β (IL-1β) IL-18 ELISA. results indicated that for TXNIP. reduce LDH MDA activities, increase CAT, GSH, T-SOD, inhibit ROS production. Mechanistically, decreased gene expressions Caspase-1, NLRP3, increasing TRX. Also, IL-1β IL-18. conclusion, against cardiomyocyte involves inhibition TXNIP/NLRP3 pathway, providing experimental evidence its potential clinical application.

Language: Английский

Citations

0
The effect and mechanism of freeze-dried powder of Poecilobdella manillensis on improving inflammatory injury of rat glomerular mesangial cells through TXNIP / NLRP3 pathway DOI Creative Commons

Xi Sun,

Maiheliya Mijiti,

Chuyin Huang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(18), P. e38206 - e38206

Published: Sept. 1, 2024

Language: Английский

Citations

0
Pyroptosis in Lung Cancer: The Emerging Role of Non-Coding RNAs DOI

Lakshmi Thangavelu,

Ahsas Goyal, Muhammad Afzal

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 263, P. 155619 - 155619

Published: Sept. 28, 2024

Language: Английский

Citations

0
Inhibition of IRE1α/XBP1 axis alleviates LPS-induced acute lung injury by suppressing TXNIP/NLRP3 inflammasome activation and ERK/p65 signaling pathway DOI Creative Commons
Sijiao Wang, Lijuan Hu, Yi‐Peng Fu

et al.

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

Published: Nov. 27, 2024

Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) is a devastating clinical with high incidence and mortality rates. IRE1α-XBP1 pathway one of the three major signaling axes endoplasmic reticulum stress that involved in inflammation, metabolism, immunity. The role potential mechanisms axis ALI/ARDS has not well understood. ALI murine model was established by intratracheal administration lipopolysaccharide (LPS). Hematoxylin eosin (H&E) staining analysis bronchoalveolar lavage fluid (BALF) were used to evaluate degree injury. Inflammatory responses assessed ELISA RT-PCR. Apoptosis evaluated using TUNEL western blot. Moreover, blot, immunohistochemistry, immunofluorescence applied test expression IRE1α, XBP1, NLRP3, TXNIP, IL-1β, ERK1/2 NF-κB p65. IRE1α significantly increased after 24 h LPS treatment. Inhibition 4µ8C notably improved LPS-induced inflammatory infiltration, reduced levels IL-6, TNF-α, decreased cell apoptosis as activation NLRP3 inflammasome. Besides, LPS-stimulated Beas-2B cells, both knockdown XBP1 diminished mRNA IL-6 IL-1B, inhibited protein secreted IL-1β. Mechanically, phosphorylation nuclear translocation p65 suppressed knockdown. In summary, our findings suggest crucial pathogenesis ALI/ARDS, whose suppression could mitigate pulmonary response through TXNIP/NLRP3 inflammasome ERK/p65 pathway. Our study may provide new evidence be promising therapeutic target for ALI/ARDS.

Language: Английский

Citations

0