The Signaling Pathways Regulating NLRP3 Inflammasome Activation

Chen, Ming-Ye; Ye, Xun-jia; He, Xian-Hui; Ouyang, Dong-Yun

doi:10.1007/s10753-021-01439-6

Cited by 80 publications

(44 citation statements)

References 151 publications

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“…There appears to be a link between AMPK, mTOR, and NLRP3 inflammasome signals, according to research. Actuation of AMPK diminishes the action of mTOR and NLRP3 [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Yuan¹,

Fan

Guo³

et al. 2022

Analytical Cellular Pathology

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Spinal cord injury (SCI) is an extreme neurological impairment with few effective drug treatments. Pyroptosis is a recently found and proven type of programmed cell death that is characterized by a reliance on inflammatory caspases and the release of a large number of proinflammatory chemicals. Pyroptosis differs from other cell death mechanisms such as apoptosis and necrosis in terms of morphological traits, incidence, and regulatory mechanism. Pyroptosis is widely involved in the occurrence and development of SCI. In-depth research on pyroptosis will help researchers better understand its involvement in the onset, progression, and prognosis of SCI, as well as provide new therapeutic prevention and treatment options. Herein, we investigated the role of AMPK-mediated activation of the NLRP3 inflammasome in the neuroprotection of MET-regulated pyroptosis. We found that MET treatment reduced NLRP3 inflammasome activation by activating phosphorylated AMPK and reduced proinflammatory cytokine (IL-1β, IL-6, and TNF-α) release. At the same time, MET improved motor function recovery in rats after SCI by reducing motor neuron loss in the anterior horn of the spinal cord. Taken together, our study confirmed that MET inhibits neuronal pyroptosis after SCI via the AMPK/NLRP3 signaling pathway, which is mostly dependent on the AMPK pathway increase, hence decreasing NLRP3 inflammasome activation.

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“…There appears to be a link between AMPK, mTOR, and NLRP3 inflammasome signals, according to research. Actuation of AMPK diminishes the action of mTOR and NLRP3 [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Yuan¹,

Fan

Guo³

et al. 2022

Analytical Cellular Pathology

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“…Interleukin-1β (IL-1β) is produced by the activation of the NLRP3 inflammasome [ 18 ]. The activation of the NLRP3 inflammasome requires two steps: priming and triggering.…”

Section: Tlr4 In the Kidneymentioning

confidence: 99%

Hypothetical Mechanism of Exercise-Induced Acute Kidney Injury Associated with Renal Hypouricemia

Hosoyamada

2021

Biomedicines

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Renal hypouricemia (RHUC) is a hereditary disease that presents with increased renal urate clearance and hypouricemia due to genetic mutations in the urate transporter URAT1 or GLUT9 that reabsorbs urates in the renal proximal tubule. Exercise-induced acute kidney injury (EIAKI) is known to be a complication of renal hypouricemia. In the skeletal muscle of RHUC patients during exhaustive exercise, the decreased release of endothelial-derived hyperpolarization factor (EDHF) due to hypouricemia might cause the disturbance of exercise hyperemia, which might increase post-exercise urinary urate excretion. In the kidneys of RHUC patients after exhaustive exercise, an intraluminal high concentration of urates in the proximal straight tubule and/or thick ascending limb of Henle’s loop might stimulate the luminal Toll-like receptor 4–myeloid differentiation factor 88–phosphoinositide 3-kinase–mammalian target of rapamycin (luminal TLR4–MyD88–PI3K–mTOR) pathway to activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and may release interleukin-1β (IL-1β), which might cause the symptoms of EIAKI.

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“…Gal-8 exerts these changes by recognizing exposed luminal glycans of the damaged membranes [22,95]. Given that activation of ERK and mTOR stimulate the NF-κB pathway [83,89,94,[96][97][98], inhibition of mTOR and the Ras-MEK-ERK pathway by intracellular Gal-8 is expected to dampen cytokine/chemokine expression and secretion.…”

Section: Effects Of Intracellular Gal-8 On Cytokine/chemokine Express...mentioning

confidence: 99%

“…However, the links between the autophagy-promoting effects of intracellular Gal-8 and its stimulatory effects on cytokine expression in vivo is largely obscure, and even might be contradictory. Given that autophagy negatively regulates the activation of inflammasomes [ 88 ] and given that inflammasomes such as the NLRP3 mediate IL-1β/IL-18 maturation and release [ 89 ], it follows that by promoting autophagy, intracellular Gal-8, might in fact inhibit activation of the NLRP3 inflammasome and the formation of at least a subset of cytokines, such as IL-1β.…”

Section: Effects Of Intracellular Gal-8 On Cytokine/chemokine Express...mentioning

confidence: 99%

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Galectin-8, cytokines, and the storm

Zick

2021

Biochemical Society Transactions

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Galectin-8 (Gal-8) belongs to a family of animal lectins that modulate cell adhesion, cell proliferation, apoptosis, and immune responses. Recent studies have shown that mammalian Gal-8 induces in an autocrine and paracrine manner, the expression and secretion of cytokines and chemokines such as RANKL, IL-6, IL-1β, SDF-1, and MCP-1. This involves Gal-8 binding to receptor complexes that include MRC2/uPAR/LRP1, integrins, and CD44. Receptors ligation triggers FAK, ERK, Akt, and the JNK signaling pathways, leading to induction of NF-κB that promotes cytokine expression. Indeed, immune-competent Gal-8 knockout (KO) mice express systemic lower levels of cytokines and chemokines while the opposite is true for Gal-8 transgenic animals. Cytokine and chemokine secretion, induced by Gal-8, promotes the migration of cancer cells toward cells expressing this lectin. Accordingly, Gal-8 KO mice experience reduced tumor size and smaller and fewer metastatic lesions when injected with cancer cells. These observations suggest the existence of a ‘vicious cycle’ whereby Gal-8 expression and secretion promotes the secretion of cytokines and chemokines that further promote Gal-8 expression. This ‘vicious cycle’ could enhance the development of a ‘cytokine storm’ which is a key contributor to the poor prognosis of COVID-19 patients.

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The Signaling Pathways Regulating NLRP3 Inflammasome Activation

Cited by 80 publications

References 151 publications

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Hypothetical Mechanism of Exercise-Induced Acute Kidney Injury Associated with Renal Hypouricemia

Galectin-8, cytokines, and the storm

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