Inhibition of Dectin-1 in mice ameliorates cardiac remodeling by suppressing NF-κB/NLRP3 signaling after myocardial infarction

Li, Xin; Bian, Yu; Pang, Ping; Yu, Shuting; Wang, Xiuzhu; Gao, Yuelin; Liu, Kuiwu; Liu, Qian; Yuan, Ye; Du, Weijie

doi:10.1016/j.intimp.2019.106116

Cited by 28 publications

(19 citation statements)

References 42 publications

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“…The synergistic inhibition together, at least partly, contributed to the suppression of NF‐κB transcription and led to subsequent reduction of pro‐IL‐1β expression. Accumulating evidence indicates that NF‐κB regulates NLRP3 inflammasome in different cell types, such as epithelia, cardiomyocyte, cancer cells, and Mϕs 46–49 . In addition to the canonical NLRP3 inflammasome activation, there is another noncanonical activation that targets caspase‐11, which directly induce canonical NLRP3 inflammasome activation by binding NF‐κB, leading to the proteolysis and activation of pro‐caspase‐1 to form active caspase‐1 dimers 50,51 .…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1

Yin

Gao

Tao

et al. 2020

Journal of Leukocyte Biology

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LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti‐nociceptive property, but its effect on LPS‐induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analgesic effect of PF on an inflammatory pain mouse model and explore the underlying mechanisms. LPS‐induced inflammatory pain model was established in C57BL/6J mice after PF treatment. Then, thermal hyperalgesia, neutrophil infiltration, inflammatory cytokine production, intracellular Ca2+ levels, PKC activity, transient receptor potential vanilloid 1 (TRPV‐1) expression, NF‐κB transcription, and NLPR3 inflammasome activation were assessed by thermal withdrawal latency, histopathology, ELISA, intracellular Ca2+ concentration, immunohistochemistry, and Western blot, separately. PF significantly relieved inflammatory pain and paw edema in mice with LPS‐induced inflammatory pain. Additionally, PF inhibited neutrophil infiltration, inflammatory cytokine production (IL‐1β, TNF‐α, and IL‐6), intracellular Ca2+ levels, and PKC activity as well as suppressed TRPV‐1 expression, NF‐κB transcription, and NLPR3 inflammasome activation in the footpad tissue samples. Importantly, capsaicin (TRPV‐1 agonists) obviously reversed the pain‐relieving effect of PF, suggesting the involvement of TRPV‐1 in the analgesic activity of PF. Our results indicated PF ameliorated LPS‐induced inflammation and pain in mice by inhibiting TRPV‐1‐mediated NLRP3 inflammasome activation. These findings suggest that PF can be as a potential pharmacological agent for inflammatory pain and thus deserves more attention and further investigation.

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Section: Discussionmentioning

confidence: 99%

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1

Yin

Gao

Tao

et al. 2020

Journal of Leukocyte Biology

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“…Laminarin, a dectin-1 antagonist, reduced the number of IBA1-positive cells and the expression of tumor necrosis factor and induced nitric oxide synthase on the third day after ischemic stroke, which reduced the volume of cerebral infarction and improved nerve function [14]. Upregulation of dectin-1 in myocardial cells after ischemiareperfusion injury promoted cardiac remodeling by activating NF-κB and NLRP3 [15]. Dectin-1 can cause demyelination and axonal injury in a macrophage-dependent way, and the dectin-1-null knockout animal model showed that the dieback of axons was also reduced after spinal cord injury [16].…”

Section: Discussionmentioning

confidence: 99%

The Role of Dectin-1-Mediated M1 Macrophage Polarization in Cerebral Ischemia-Reperfusion Injury

Chen

Lin

Ding

et al. 2021

Emergency Medicine International

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Introduction. The advances in cerebral ischemia treatment have resulted in a larger proportion of patients get the benefits of rebuilding blood flow to the brain. Then, ischemia-reperfusion injury has emerged as a new essential problem. Dectin-1 plays an important role in cerebral ischemia-reperfusion injury by regulating the function of immune cells. Methods. C57BL/6 was blindly divided into four groups including the sham-operated group and the three different kinds of middle cerebral artery occlusion (MCAO) groups (after 6 hours, 12 hours, and 24 hours after plug removal). The protein expression levels of dectin-1, proapoptosis molecule, and antiapoptosis molecule were measured by using western blot analysis. The brain tissue was analyzed by flow cytometry to detect the M1 macrophage levels. Results. The correlation analysis of dectin-1 and infarct areas showed that there was an obviously positive correlation in between them (R = 0.9603). Dectin-1, cleaved caspase-3, and Bax increased, while antiapoptosis molecule, Bcl-2, decreased at three appropriate time points (after 6 hours, 12 hours, and 24 hours). The level of M1 macrophages in the experimental group increased after ischemia-reperfusion injury compared to the control group. Conclusions. The high expression level of dectin-1 may affect M1 macrophage polarization and brain cell apoptosis in cerebral ischemia-reperfusion injury.

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“…Hoechst 33342 and propidium iodide (PI) fluorescent staining were performed as previously described ( Li et al, 2020 ). The neonatal CMs were seeded in 24-well plates at a density of 1.0 × 10 5 /well.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as previously described ( Li et al, 2020 ). Total tissue/cell proteins were extracted using a lysis buffer (Roche, Switzerland) containing 1% protease inhibitor and 10% phosphatase inhibitor.…”

Section: Methodsmentioning

confidence: 99%

Mettl14 Attenuates Cardiac Ischemia/Reperfusion Injury by Regulating Wnt1/β-Catenin Signaling Pathway

Pang

et al. 2021

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) methylation in RNA is a dynamic and reversible modification regulated by methyltransferases and demethylases, which has been reported to participate in many pathological processes of various diseases, including cardiac disorders. This study was designed to investigate an m6A writer Mettl14 on cardiac ischemia–reperfusion (I/R) injury and uncover the underlying mechanism. The m6A and Mettl14 protein levels were increased in I/R hearts and neonatal mouse cardiomyocytes upon oxidative stress. Mettl14 knockout (Mettl14+/−) mice showed pronounced increases in cardiac infarct size and LDH release and aggravation in cardiac dysfunction post-I/R. Conversely, adenovirus-mediated overexpression of Mettl14 markedly reduced infarct size and apoptosis and improved cardiac function during I/R injury. Silencing of Mettl14 alone significantly caused a decrease in cell viability and an increase in LDH release and further exacerbated these effects in the presence of H2O2, while overexpression of Mettl14 ameliorated cardiomyocyte injury in vitro. Mettl14 resulted in enhanced levels of Wnt1 m6A modification and Wnt1 protein but not its transcript level. Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and β-catenin proteins, whereas Mettl14+/− hearts exhibited the opposite results. Knockdown of Wnt1 abrogated Mettl14-mediated upregulation of β-catenin and protection against injury upon H2O2. Our study demonstrates that Mettl14 attenuates cardiac I/R injury by activating Wnt/β-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.

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Inhibition of Dectin-1 in mice ameliorates cardiac remodeling by suppressing NF-κB/NLRP3 signaling after myocardial infarction

Cited by 28 publications

References 42 publications

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1

The Role of Dectin-1-Mediated M1 Macrophage Polarization in Cerebral Ischemia-Reperfusion Injury

Mettl14 Attenuates Cardiac Ischemia/Reperfusion Injury by Regulating Wnt1/β-Catenin Signaling Pathway

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