NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression

Li, Shanshan; Sun, Yiming; Song, Mengmeng; Song, Yuting; Fang, Yinquan; Zhang, Qingyu; Li, Xueting; Song, Nanshan; Ding, Jingzhong; Lu, Ming; Hu, Gang

doi:10.1172/jci.insight.146852

Cited by 141 publications

(71 citation statements)

References 54 publications

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“…A hypothesis was arisen that NLRP3 inflammasome may closely link with pyroptosis. In fact, a plenty of research results confirm the hypothesis in term of coexistence between activation of NLRP3 inflammasome and occurrence of pyroptosis in organism [ 103 ][ 104 ][ 105 ][ 106 ][ 107 ][ 108 ][ 109 ]. Many in-depth studies have found the molecular mechanism of NLRP3 inflammasome in relation to pyroptosis.…”

Section: Relation Between Nlrp3 Inflammasome and Pyroptosismentioning

confidence: 71%

“…Specifically, NLRP3 inflammasome assembly promote pro-caspase-1 activation into active caspase-1, which accelerate pro-inflammatory factor release and GSDMD pore formation in cell membrane, and further induce pyroptosis [ 103 ]. NLRP3 inhibitors can alleviate or reverse the activation of NLRP3 inflammasome-mediated pyroptosis [ 104 ][ 105 ][ 106 ][ 107 ][ 108 ][ 109 ]. Blocking NLRP3 and pyroptosis is a new and effective strategy to inhibit inflammation and its related diseases, which may provide a unique perspective to deeply understand the relationship between NLRP3 inflammasome and pyroptosis [ 110 ].…”

Section: Relation Between Nlrp3 Inflammasome and Pyroptosismentioning

confidence: 99%

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Pyroptosis in NLRP3 inflammasome-related atherosclerosis

Zeng¹,

Liu²,

Huo³

et al. 2022

CST

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Pyroptosis is a proinflammatory form of programmed cell death in response to inﬂammation. It involves in the pathogenesis and outcomes of atherosclerosis characterized by NLRP3 inflammasome assembly, membrane pore formation, cell swelling, pro-inflammatory mediator and cytokine release. There are known pyroptosis molecular pathways including the caspase-1 depended canonical signaling pathway and the caspase-4/5/11 determined non-canonical signaling pathway. It is essential to explore the connection among NLRP3 inflammasome, pyroptosis and atherosclerosis, which may shed light on the potential therapeutic strategies that target pyroptosis in atherosclerotic treatment.

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Section: Relation Between Nlrp3 Inflammasome and Pyroptosismentioning

confidence: 71%

Section: Relation Between Nlrp3 Inflammasome and Pyroptosismentioning

confidence: 99%

Pyroptosis in NLRP3 inflammasome-related atherosclerosis

Zeng¹,

Liu²,

Huo³

et al. 2022

CST

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“…Pyroptosis is a unique type of programed cell death depending on inflammatory caspase–mediated activation of GSDMD ( Li et al, 2021 ). Activated GSDMD protein formed the pore in the cell membrane, causing cellular swell and rupture and the release of proinflammatory IL-1β and IL-18 ( Ding et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that caspase-1 activation is initiated by the assembly of the NLRP3 inflammasome, comprised of NLRP3, ASC, and caspase-1, and activated caspase-1 promoted the secretion of mature IL-1β and IL-18 to amplify the inflammatory response ( Li et al, 2021 ; Sun et al, 2022 ). We previously reported the increase of NLRP3 signaling in TCE-induced kidney damage ( Xie et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Membrane Attack Complex C5b-9 Promotes Renal Tubular Epithelial Cell Pyroptosis in Trichloroethylene-Sensitized Mice

et al. 2022

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Trichloroethylene (TCE), a commonly used organic solvent, is known to cause trichloroethylene hypersensitivity syndrome (THS), also called occupational medicamentosa–like dermatitis due to TCE (OMDT) in China. OMDT patients presented with severe inflammatory kidney damage, and we have previously shown that the renal damage is related to the terminal complement complex C5b-9. Here, we sought to determine whether C5b-9 participated in TCE-induced immune kidney injury by promoting pyroptosis, a new form of programed cell death linked to inflammatory response, with underlying molecular mechanisms involving the NLRP3 inflammasome. A BALB/c mouse-based model of OMDT was established by dermal TCE sensitization in the presence or absence of C5b-9 inhibitor (sCD59-Cys, 25μg/mouse) and NLRP3 antagonist (MCC950, 10 mg/kg). Kidney histopathology, renal function, expression of inflammatory mediators and the pyroptosis executive protein gasdermin D (GSDMD), and the activation of pyroptosis canonical NLRP3/caspase-1 pathway were examined in the mouse model. Renal tubular damage was observed in TCE-sensitized mice. GSDMD was mainly expressed on renal tubular epithelial cells (RTECs). The caspase-1–dependent canonical pathway of pyroptosis was activated in TCE-induced renal damage. Pharmacological inhibition of C5b-9 could restrain the caspase-1–dependent canonical pathway and rescued the renal tubular damage. Taken together, our results demonstrated that complement C5b-9 plays a central role in TCE-induced immune kidney damage, and the underlying mechanisms involve NLRP3-mediated pyroptosis.

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“…Depressive mice were shown to present astrocytic loss that was promoted by pyroptotic cellular death. The pyroptotic process was triggered by the activation of the NLRP3/caspase-1/GSDMD pathway ( Li et al, 2021 ). Also, in mice with depression induced by chronic mild stress, it was reported that kynurenine, a tryptophan metabolite, acted as a pro-inflammatory factor in astrocytes.…”

Section: Inflammasomes and Astrocytesmentioning

confidence: 99%

Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities

Mata-Martínez

Dı́az-Muñoz

Vázquez‐Cuevas

2022

Front. Cell. Neurosci.

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Inflammation mediated by the innate immune system is a physiopathological response to diverse detrimental circumstances such as microbe infections or tissular damage. The molecular events that underlie this response involve the assembly of multiprotein complexes known as inflammasomes. These assemblages are essentially formed by a stressor-sensing protein, an adapter protein and a non-apoptotic caspase (1 or 11). The coordinated aggregation of these components mediates the processing and release of pro-inflammatory interleukins (IL-β and IL-18) and cellular death by pyroptosis induction. The inflammatory response is essential for the defense of the organism; for example, it triggers tissue repair and the destruction of pathogen microbe infections. However, when inflammation is activated chronically, it promotes diverse pathologies in the lung, liver, brain and other organs. The nervous system is one of the main tissues where the inflammatory process has been characterized, and its implications in health and disease are starting to be understood. Thus, the regulation of inflammasomes in specific cellular types of the central nervous system needs to be thoroughly understood to innovate treatments for diverse pathologies. In this review, the presence and participation of inflammasomes in pathological conditions in different types of glial cells will be discussed.

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NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression

Cited by 141 publications

References 54 publications

Pyroptosis in NLRP3 inflammasome-related atherosclerosis

Pyroptosis in NLRP3 inflammasome-related atherosclerosis

Membrane Attack Complex C5b-9 Promotes Renal Tubular Epithelial Cell Pyroptosis in Trichloroethylene-Sensitized Mice

Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities

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