NLRP3 inflammasome inhibition attenuates subacute neurotoxicity induced by acrylamide in vitro and in vivo

Sui, Xin; Yang, Jun; Zhang, Guangzhou; Yuan, Xiaofeng; Li, Wan-hua; Long, Jianhai; Luo, Yuan; Li, Yunfeng; Wang, Yongan

doi:10.1016/j.tox.2020.152392

Cited by 34 publications

(26 citation statements)

References 42 publications

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“…Downstream NLRP3 activation markers were determined in response to acrylamide treatment, and MCC950 incubation reversed these proinflammatory readouts. These results were verified in a murine model of acrylamide exposure, in which treatment with MCC950 or NLRP3 deletion significantly ameliorated acrylamide-induced ataxia, cerebellar Purkinje cell degeneration, and apoptosis (Sui et al, 2020b).…”

Section: B Nod-like Receptor Family Pyrin Domain Containing 3 Pathology By Organmentioning

confidence: 60%

Pharmacological Inhibition of the Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome with MCC950

2021

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Section: B Nod-like Receptor Family Pyrin Domain Containing 3 Pathology By Organmentioning

confidence: 60%

Pharmacological Inhibition of the Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome with MCC950

2021

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“…We observed that the damaging responses to radiation were attenuated in NLRP3−/− mice, suggesting NLRP3 involvement in RIE-induced damage. Furthermore, MCL treatment reduced the expression of Casp1 p20 and GSDMD-N, thereby inhibiting pyroptosis in RIE, suggesting that the therapeutic effects of MCL may be mediated by inhibition of the NLRP3 inflammasome ( Gong et al, 2019 ; Sui et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Autophagy Induced by Micheliolide Alleviates Acute Irradiation-Induced Intestinal Injury via Inhibition of the NLRP3 Inflammasome

Shen

Jin

et al. 2022

Front. Pharmacol.

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Radiation-induced enteropathy (RIE) is one of the most common and fatal complications of abdominal radiotherapy, with no effective interventions available. Pyroptosis, a form of proinflammatory regulated cell death, was recently found to play a vital role in radiation-induced inflammation and may represent a novel therapeutic target for RIE. To investigate this, we found that micheliolide (MCL) exerted anti-radiation effects in vitro. Therefore, we investigated both the therapeutic effects of MCL in RIE and the possible mechanisms by which it may be therapeutic. We developed a mouse model of RIE by exposing C57BL/6J mice to abdominal irradiation. MCL treatment significantly ameliorated radiation-induced intestinal tissue damage, inflammatory cell infiltration, and proinflammatory cytokine release. In agreement with these observations, the beneficial effects of MCL treatment in RIE were abolished in Becn1+/− mice. Furthermore, super-resolution microscopy revealed a close association between NLR pyrin domain three and lysosome-associated membrane protein/light chain 3-positive vesicles following MCL treatment, suggesting that MCL facilitates phagocytosis of the NLR pyrin domain three inflammasome. In summary, MCL-mediated induction of autophagy can ameliorate RIE by NLR pyrin domain three inflammasome degradation and identify MCL as a novel therapy for RIE.

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“…IL-18, as a co-factor in synergism with IL-12, exerts a potent pro-inflammatory effect via stimulating the production of gamma interferon (INF-γ) in Th1 cells [ 37 ]. Cleaved caspase-1, which could be activated by NLRP3 inflammasome, a large intracellular multiprotein complex containing caspase-1, ASC and NLRP3, is crucial for the transformation of IL-1β and IL-18 from precursor form to mature form, which could further trigger the downstream signaling pathways [ 38 , 39 ]. It has been reported that MCC950, a kind of the NLRP3 inflammasome inhibitor, could against neuroinflammation and had a neuroprotective effect which might be associated with reduced activation of microglial, recruitment of leukocyte, and production of pro-inflammatory cytokines [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

RKC-B1 Blocks Activation of NF-κB and NLRP3 Signaling Pathways to Suppress Neuroinflammation in LPS-Stimulated Mice

et al. 2021

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RKC-B1 is a novel fermentation product obtained from the marine micromonospora FIM02-523A. Thus far, there have been few reports about the pharmacological activity of RKC-B1. In our present study, we investigated the anti-neuroinflammatory effects and the possible mechanism of RKC-B1 in LPS-stimulated mice. After treatment with RKC-B1, RNA-seq transcriptome of the cerebral cortex tissue was conducted to find the differentially expressed genes (DEGs). Inflammatory cytokines and proteins were evaluated by ELISA and WB. In RNA-seq analysis, there were 193 genes screened as core genes of RKC-B1 for treatment with neuroinflammation. The significant KEGG enrichment signaling pathways of these core genes were mainly included TNF signaling pathway, IL-17 signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway and others. The corresponding top five KEGG enrichment pathways of three main clusters in PPI network of core genes were closely related to human immune system and immune disease. The results showed that RKC-B1 reduced the levels of pro-inflammatory factors (IL-6, IL-1β, MCP-1, and ICAM-1) and the expression of COX2 in cerebral cortex tissue. Additionally, we found that the anti-neuroinflammation activity of RKC-B1 might be related to suppress activating of NF-κB and NLRP3/cleaved caspase-1 signaling pathways. The current findings suggested that RKC-B1 might be a promising anti-neuroinflammatory agent.

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NLRP3 inflammasome inhibition attenuates subacute neurotoxicity induced by acrylamide in vitro and in vivo

Cited by 34 publications

References 42 publications

Pharmacological Inhibition of the Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome with MCC950

Pharmacological Inhibition of the Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome with MCC950

Autophagy Induced by Micheliolide Alleviates Acute Irradiation-Induced Intestinal Injury via Inhibition of the NLRP3 Inflammasome

RKC-B1 Blocks Activation of NF-κB and NLRP3 Signaling Pathways to Suppress Neuroinflammation in LPS-Stimulated Mice

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