Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients

Ulrich, Christof; Kneser, Leonie; Fiedler, Roman; Beckert, Julia; Wildgrube, Susann; Seibert, Eric; Fick, Sylvia; Schäfer, Christoph; Markau, Silke; Trojanowicz, Bogusz; Girndt, Matthias

doi:10.3390/toxins13120839

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…NLRP3 inflammasome activation results in caspase-1 activation, in turn causing cleavage of pro-IL-1β and gasdermin D (GSDMD). Active GSDMD aggregates and forms pores in the cell membrane, resulting in cell swelling and a programmed cell death which is called pyroptosis [ 17 ]. Pyroptosis is implicated in the pathogenesis of several neuropsychiatric disorders, such as multiple sclerosis (MS), Alzheimer’s disease, TBI, drug use disorder, and depression [ 18 , 19 ].…”

Section: Nlrp Inflammasomementioning

confidence: 99%

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

et al. 2022

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The NLRP inflammasome is a multi-protein complex which mainly consists of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain. Its activation is linked to microglial-mediated neuroinflammation and partial neuronal degeneration. Many neuropsychiatric illnesses have increased inflammatory responses as both a primary cause and a defining feature. The NLRP inflammasome inhibition delays the progression and alleviates the deteriorating effects of neuroinflammation on several neuropsychiatric disorders. Evidence on the central effects of the NLRP inflammasome potentially provides the scientific base of a promising drug target for the treatment of neuropsychiatric disorders. This review elucidates the classification, composition, and functions of the NLRP inflammasomes. It also explores the underlying mechanisms of NLRP inflammasome activation and its divergent role in neuropsychiatric disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, depression, drug use disorders, and anxiety. Furthermore, we explore the treatment potential of the NLRP inflammasome inhibitors against these disorders.

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Section: Nlrp Inflammasomementioning

confidence: 99%

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

et al. 2022

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“…Furthermore, we have to keep in mind that caspase-4 activity can also be induced by other molecules. In a recent paper, we demonstrated that caspase-4 activity can be induced by a high concentration (1mmolar) of uremic toxin indoxyl sulfate in the monocytic THP-1 cell line [32]. It seems plausible that if these results can be stably transferred from THP-1 cells to PBMCs of CKD patients, caspase-4 activity can be stimulated by quite different substances.…”

Section: Discussionmentioning

confidence: 89%

Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4

Ulrich,

Canim,

Herberger

et al. 2023

IJMS

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Hypervolemia is associated with inflammation in hemodialysis (HD) patients. How hypervolemia triggers inflammation is not entirely known. We initiated a cross-sectional study enrolling 40 hemodialysis patients who were categorized into normovolemic (N; 23) and hypervolemic (H; 17) groups by bioimpedance measurement. A caspase activity assay in combination with a specific caspase-4 inhibitor was used to detect caspase-4 activity in isolated peripheral blood mononuclear cells (PBMCs). Transcription factors RelA (pS529) and RelB (pS552) were analyzed by phospho-flow cytometry. Serum endotoxins were detected by an amebocyte lysate-based assay, and IL-6 (interleukin-6) and TNF-α (Tumor necrosis factor-α) gene expression were detected using the ELISA technique. Hypervolemic patients were older, more frequently had diabetes and showed increased CRP and IL-6 levels. Caspase-4 activity, which is linked to intracellular endotoxin detection, was significantly elevated in H patients. While the frequency of RelA-expressing immune cells and the expression density in these cells did not differ, the monocytic frequency of cells positively stained for RelB (pS552) was significantly decreased in H patients. Increased caspase-4 activity in H patients may indicate a cause of inflammation in H patients. The post-translational modification of RelB (pS552) is linked to downregulation of NF-kB activity and may indicate the resolution of inflammation, which is more distinct in N patients compared to H patients. Therefore, both higher inflammatory loads and lower inflammatory resolution capacities are characteristics of H patients.

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“…Besides GSDMD which is a co-executor of pyroptosis, other members of the gasdermin family, including GSDMA3, GSDMB, and GSDME, can also be cleaved to induce pyroptosis [ 6 ]. Studies have shown that caspase-11 and its corresponding proteases, caspase-4 and caspase-5, can trigger pyroptosis by cleaving the pyroptosis executor in the gasdermin protein family [ 86 ]. However, the complete mechanism underlying pyroptosis remains unclear.…”

Section: Effects Of Nlrp3 On Pyroptosismentioning

confidence: 99%

NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors

Xu,

Yang,

Chen

et al. 2023

Transl Neurodegener

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Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1β and IL-18) by activating caspase-1. In this review, we comprehensively describe the structure and functions of the NLRP3 inflammasome. We also explore the intrinsic relationship between the NLRP3 inflammasome and cognitive impairment, which involves immune cell activation, cell apoptosis, oxidative stress, mitochondrial autophagy, and neuroinflammation. Finally, we describe NLRP3 inflammasome antagonists as targeted therapies to improve cognitive impairment.

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Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients

Cited by 4 publications

References 37 publications

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4

NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors

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