NLRP3 inflammasome-driven IL-1β and IL-18 contribute to lipopolysaccharide-induced septic cardiomyopathy

Fujimura, Kenta; Karasawa, Tadayoshi; Komada, Takanori; Yamada, Naoya; Mizushina, Yoshiko; Baatarjav, Chintogtokh; Matsumura, Takayoshi; Otsu, Kinya; Takeda, Norihiko; Mizukami, Hiroaki; Kario, Kazuomi; Takahashi, Masafumi

doi:10.1016/j.yjmcc.2023.05.003

Cited by 20 publications

(4 citation statements)

References 32 publications

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“…In both pyroptosis and inflammation, IL-1β is a key signal [ 90 ]. Therefore, in the future, multiple monitoring pathways may lead to the development of signal probes for H. otakii to monitor reoxygenation injury.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Zhan,

Gao,

Peng

et al. 2024

Comparative Immunology Reports

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Section: Discussionmentioning

confidence: 99%

Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Zhan,

Gao,

Peng

et al. 2024

Comparative Immunology Reports

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“…NLRP3 inflammasome and Myd-88 activation have been implicated in several diseases, including cancer and cardiomyopathies ( Figure 7 ). Both induce cardiomyocyte death and exacerbate myocardial injury by promoting inflammation and fibrosis through IL-1β and IL-18, which activates macrophages and immune cells in heart tissue ( 104 ).…”

Section: Discussionmentioning

confidence: 99%

Sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents ejection fraction reduction, reduces myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity

Quagliariello,

Canale,

Bisceglia

et al. 2024

Front. Cardiovasc. Med.

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BackgroundAnthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in patients with cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i dapagliflozin administered before and during doxorubicin (DOXO) therapy could prevent cardiac dysfunction and reduce pro-inflammatory pathways in preclinical models.MethodsCardiomyocytes were exposed to DOXO alone or combined with dapagliflozin (DAPA) at 10 and 100 nM for 24 h; cell viability, iATP, and Ca++ were quantified; lipid peroxidation products (malondialdehyde and 4-hydroxy 2-hexenal), NLRP3, MyD88, and cytokines were also analyzed through selective colorimetric and enzyme-linked immunosorbent assay (ELISA) methods. Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg), or DOXO combined with DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed.ResultsDAPA exerts cytoprotective, antioxidant, and anti-inflammatory properties in human cardiomyocytes exposed to DOXO by reducing iATP and iCa++ levels, lipid peroxidation, NLRP-3, and MyD88 expression. Pro-inflammatory intracellular cytokines were also reduced. In preclinical models, DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in the DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF, and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in the DOXO group; on the other hand, their expression was reduced in the DAPA-DOXO group. Troponin-T, B-type natriuretic peptide (BNP), and N-Terminal Pro-BNP (NT-pro-BNP) were strongly reduced in the DOXO-DAPA group, revealing cardioprotective properties of SGLT2i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression.ConclusionThe overall picture of the study encourages the use of DAPA in the primary prevention of cardiomyopathies induced by anthracyclines in patients with cancer.

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“…It is noteworthy that intervention in the ALI model with anti-CD177 led to the most significant reduction in IL-1β levels in peripheral blood and BALF compared to other inflammatory cell factor levels. This indicates that IL-1β may act as a specific effector molecule in the CD177 signaling pathway and serves as an effector molecule of the NLRP3 inflammasome [ 33 , 34 ]. This finding suggests that CD177 is an activation pathway for the NLRP3 inflammasome ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

The link between neutrophils, NETs, and NLRP3 inflammasomes: The dual effect of CD177 and its therapeutic potential in acute respiratory distress syndrome/acute lung injury

Li,

Fang,

et al. 2024

Biomol Biomed

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Neutrophils are important inflammatory effector cells that protect against foreign invasion but also cause self-harm. Numerous neutrophils infiltrate the lungs in acute respiratory distress syndrome/acute lung injury (ARDS/ALI) patients. However, the exact impact of neutrophil infiltration on ARDS's onset and progression remains unclear. To investigate this, we analyzed two ARDS-related datasets from the Gene Expression Omnibus public database and discovered an association between CD177, a neutrophil-specific surface protein, and ARDS progression. We used quantitative flow cytometry to assess CD177+ neutrophils in the peripheral blood of clinical ARDS patients versus healthy controls, finding a significant increase in CD177+ neutrophils percentage among total neutrophils in ARDS patients. This finding was further confirmed in ALI mouse models. Subsequent animal experiments showed that anti-CD177 effectively reduces pulmonary edema, neutrophil infiltration, and inflammatory cytokine release, along with a decrease in reactive oxygen species (ROS) and myeloperoxidase (MPO) levels. We also established an in vitro co-culture system to mimic neutrophil and lung epithelial cell interactions. In the anti-CD177 group, we observed decreased expression of NLRP3, caspase 1, PAD4, MPO, and ROS, along with a reduction in certain inflammatory cytokines. These results indicate a crucial role for the CD177 gene in ARDS's development and progression. Inhibiting CD177 may help mitigate excessive activation of NLRP3 inflammasomes, ROS, and neutrophil extracellular traps, thus alleviating ARDS.

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NLRP3 inflammasome-driven IL-1β and IL-18 contribute to lipopolysaccharide-induced septic cardiomyopathy

Cited by 20 publications

References 32 publications

Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents ejection fraction reduction, reduces myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity

The link between neutrophils, NETs, and NLRP3 inflammasomes: The dual effect of CD177 and its therapeutic potential in acute respiratory distress syndrome/acute lung injury

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