Gasdermins pore cell membrane to pyroptosis

Liang, Huanhuan; Liu, Yingfang

doi:10.1007/s11427-016-0243-4

Cited by 17 publications

(12 citation statements)

References 17 publications

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“…Our conclusion that P.falciparum infections induce alteration in the chromatin landscape of monocytes is further supported by the observation that DE genes in Fulani monocytes often cluster in regions. Interestingly, one of these regions, 8q24.3 contains: the c-Myc gene; GSDMD, encoding inflammasome substrate gasdermin D ( Liang and Liu, 2016 ); and a novel, uncharacterised locus of resistance to severe malaria ( Malaria Genomic Epidemiology Network et al, 2015 ). Taken together we suggest that genome wide chromatin alterations occur as a result of P.falciparum infection in monocytes from Fulani, enabling a heightened transcriptional response.…”

Section: Discussionmentioning

confidence: 99%

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria

Quin

Bujila

Chérif

et al. 2017

eLife

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The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria, as reflected by fewer symptomatic cases of malaria, lower infection rates, and lower parasite densities compared to sympatric ethnic groups. However, the basis for this lower susceptibility to malaria by the Fulani is unknown. The incidence of classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations, and targeted SNP analyses of other candidate genes involved in the immune response to malaria have not been able to account for the observed difference in the Fulani susceptibility to P.falciparum. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani to elucidate the mechanisms that confer the lower susceptibility to P.falciparum malaria. When we compared uninfected and infected Fulani individuals, in contrast to uninfected and infected individuals from the sympatric ethnic group Mossi, we observed a key difference: a strong transcriptional response was only detected in the monocyte fraction of the Fulani, where over 1000 genes were significantly differentially expressed upon P.falciparum infection.

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Section: Discussionmentioning

confidence: 99%

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria

Quin

Bujila

Chérif

et al. 2017

eLife

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“…NLRP3 interacts with pro-caspase-1 upon connection with the apoptosis-associated speck-like protein containing the CARD (ASC) adapter, leading to the cleavage of precursors of inflammatory cytokines into mature forms, including interleukin-18 (IL-18) and interleukin-1β (IL-1β) ( He et al, 2016 ). Activated caspase-1 subsequently cleaves and releases the N-domain of gasdermin D (GSDMD), which eventually forms membrane pores and releases mature inflammatory mediators into the extracellular space, causing a severe inflammatory cascade reaction ( Liang and Liu, 2016 ). Studies have shown that inflammation-related pyroptosis is an important factor affecting stroke prognosis ( Jin et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Melatonin Enhances the Therapeutic Effect of Plasma Exosomes Against Cerebral Ischemia-Induced Pyroptosis Through the TLR4/NF-κB Pathway

Wang

Zhang

et al. 2020

Front. Neurosci.

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Introduction: Ischemic stroke-induced inflammation and inflammasome-dependent pyroptotic neural death cause serious neurological injury. Nano-sized plasma exosomes have exhibited therapeutic potential against ischemia and reperfusion injury by ameliorating inflammation. To enhance its therapeutic potential in patients with ischemic injury, we isolated exosomes from melatonin-treated rat plasma and assessed the neurological protective effect in a rat model of focal cerebral ischemia. Methods: Basal plasma exosomes and melatonin-treated plasma exosomes were isolated and intravenously injected into a rat model of focal cerebral ischemia. Neurological recovery was evaluated by determining the modified neurological severity score (mNSS), infarct volume, and brain water content. Pyroptosis in the ischemic cortex was detected through dUTP nick-end labeling (TUNEL) assay, lactate dehydrogenase (LDH) release, and gasdermin D (GSDMD) cleavage. NLRP3 inflammasome assembly and global inflammatory cytokine secretion were detected by enzyme-linked immunosorbent assay (ELISA) and Western blot assay. In immunized Sprague-Dawley rats, microglia pyroptosis was determined through a positive percentage of IBA1 + and caspase-1 (p20) + cells. Finally, the microRNA (miRNA) profiles in melatonin-treated plasma exosomes were analyzed by exosome miRNA microarray analysis. Results: Melatonin treatment enhanced plasma exosome therapeutic effects against ischemia-induced inflammatory responses and inflammasome-mediated pyroptosis. In addition, we confirmed that ischemic stroke-induced pyroptotic cell death occurred in the microglia and neuron, while the administration of melatonin-treated exosomes further effectively decreased the infarct volume and improved recovery of function via regulation of the TLR4/NF-κB signaling pathway. Finally, the altered miRNA profiles in the melatonin-treated plasma exosomes demonstrated the regulatory mechanisms involved in neurological recovery after ischemic injury.

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“…The formation of pores destroys cell potential energy penetration, leading to cell swelling and eventually cell pyroptosis. IL-1β is also released from cells through the pores, causing a robust inflammatory response ( 43 , 72 , 73 ).…”

Section: Molecular Mechanism Of Pyroptosismentioning

confidence: 99%

Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

2021

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Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD) in many developed and developing countries. Pyroptosis is a recently discovered form of programmed cell death (PCD). With progress in research on DKD, researchers have become increasingly interested in elucidating the role of pyroptosis in DKD pathogenesis. This review focuses on the three pathways of pyroptosis generation: the canonical inflammasome, non-canonical inflammasome, and caspase-3-mediated inflammasome pathways. The molecular and pathophysiological mechanisms of the pyroptosis-related inflammasome pathway in the development of DKD are summarized. Activation of the diabetes-mediated pyroptosis-related inflammasomes, such as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Toll-like receptor 4 (TLR4), caspase-1, interleukin (IL)-1β, and the IL-18 axis, plays an essential role in DKD lesions. By inhibiting activation of the TLR4 and NLRP3 inflammasomes, the production of caspase-1, IL-1β, and IL-18 is inhibited, thereby improving the pathological changes associated with DKD. Studies using high-glucose–induced cell models, high-fat diet/streptozotocin-induced DKD animal models, and human biopsies will help determine the spatial and temporal expression of DKD inflammatory components. Recent studies have confirmed the relationship between the pyroptosis-related inflammasome pathway and kidney disease. However, these studies are relatively superficial at present, and the mechanism needs further elucidation. Linking these findings with disease activity and prognosis would provide new ideas for DKD research.

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Gasdermins pore cell membrane to pyroptosis

Cited by 17 publications

References 17 publications

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria

Melatonin Enhances the Therapeutic Effect of Plasma Exosomes Against Cerebral Ischemia-Induced Pyroptosis Through the TLR4/NF-κB Pathway

Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

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