Commentary: p31-43 Gliadin Peptide Forms Oligomers and Induces NLRP3 Inflammasome/Caspase 1- Dependent Mucosal Damage in Small Intestine

Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1β into mature IL-1β, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of Glycyrrhiza species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1β in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1β in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1β protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1β. NLRP3–/– and caspase-1–/– mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3–/– and caspase-1–/– mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation.

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Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Infection and Immunity ◽

10.1128/iai.00354-13 ◽

2013 ◽

Vol 81 (8) ◽

pp. 2997-3008 ◽

Cited By ~ 4

Author(s):

Wei Li ◽

Barry P. Katz ◽

Margaret E. Bauer ◽

Stanley M. Spinola

Keyword(s):

Nlrp3 Inflammasome ◽

Interleukin 1 ◽

Study Data ◽

Human Infection ◽

Haemophilus Ducreyi ◽

Inflammasome Activation ◽

Microbial Infection ◽

Content Type ◽

Ulcer Disease ◽

Caspase 1

ABSTRACTRecognition of microbial infection by certain intracellular pattern recognition receptors leads to the formation of a multiprotein complex termed the inflammasome. Inflammasome assembly activates caspase-1 and leads to cleavage and secretion of the proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-18, which help control many bacterial pathogens. However, excessive inflammation mediated by inflammasome activation can also contribute to immunopathology. Here, we investigated whetherHaemophilus ducreyi, a Gram-negative bacterium that causes the genital ulcer disease chancroid, activates inflammasomes in experimentally infected human skin and in monocyte-derived macrophages (MDM). AlthoughH. ducreyiis predominantly extracellular during human infection, several inflammasome-related components were transcriptionally upregulated inH. ducreyi-infected skin. Infection of MDM with live, but not heat-killed,H. ducreyiinduced caspase-1- and caspase-5-dependent processing and secretion of IL-1β. Blockage ofH. ducreyiuptake by cytochalasin D significantly reduced the amount of secreted IL-1β. Knocking down the expression of the inflammasome components NLRP3 and ASC abolished IL-1β production. Consistent with NLRP3-dependent inflammasome activation, blocking ATP signaling, K+efflux, cathepsin B activity, and lysosomal acidification all inhibited IL-1β secretion. However, inhibition of the production and function of reactive oxygen species did not decrease IL-1β production. Polarization of macrophages to classically activated M1 or alternatively activated M2 cells abrogated IL-1β secretion elicited byH. ducreyi. Our study data indicate thatH. ducreyiinduces NLRP3 inflammasome activation via multiple mechanisms and suggest that the heterogeneity of macrophages within human lesions may modulate inflammasome activation during human infection.

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Activation of AMPK/mTOR-driven autophagy and inhibition of NLRP3 inflammasome by saxagliptin ameliorate ethanol-induced gastric mucosal damage

Life Sciences ◽

10.1016/j.lfs.2021.119743 ◽

2021 ◽

pp. 119743

Author(s):

Hany H. Arab ◽

Ahmed M. Ashour ◽

Amany M. Gad ◽

Ayman M. Mahmoud ◽

Ahmed M. Kabel

Keyword(s):

Nlrp3 Inflammasome ◽

Mucosal Damage ◽

Gastric Mucosal Damage

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LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition

Nature Communications ◽

10.1038/ncomms3075 ◽

2013 ◽

Vol 4 (1) ◽

Cited By ~ 49

Author(s):

Jing Jin ◽

Qian Yu ◽

Chaofeng Han ◽

Xiang Hu ◽

Sheng Xu ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammasome Activation ◽

Caspase 1 ◽

Nlrp3 Inflammasome Activation

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Effect of luteolin on the gene level expression of apoptosis-associated speck-like protein containing a caspase recruitment domain of NLRP3 inflammasome and NF-κB in rats subjected to experimental pancreatitis – influence of HSP70

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0255 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Sadanandan Rajapriya ◽

Arumugam Geetha

Keyword(s):

Body Weight ◽

Nlrp3 Inflammasome ◽

Rank Correlation ◽

Experimental Period ◽

Serum Levels ◽

Normal Diet ◽

Experimental Pancreatitis ◽

Caspase 1 ◽

Spearman’S Rank Correlation ◽

Pyrin Domain

Abstract Objectives Nod-like receptor pyrin domain containing 3 (NLRP3) is one of the well characterized inflammasome that controls the maturation of pro-inflammatory cytokines and thereby the inflammation in pancreas which could be a promising target for anti-inflammatory drugs. The present study is aimed to explore whether luteolin can target the NLRP3 inflammasome and modulate its activity through the signaling protein, HSP70 in the ethanol-cerulein model of experimental pancreatitis. Methods Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats received normal diet. Groups 3 and 4 rats received isocalorically adjusted diet containing ethanol for 5 weeks and cerulein (20 μg/kg body weight i.p., thrice weekly for the last 3 weeks of the experimental period). Additionally, group 2 and 4 rats received 2 mg/kg body weight of luteolin orally from third week. Results Luteolin co-administration decreased the serum levels of HSP70, oxidative stress markers, myeloperoxidase, GSH/GSSG and GST with concomitant downregulation in the mRNA expression of HSP70, caspase-1, ASC-NLRP3 and NF-κB. Spearman’s rank correlation test showed that serum HSP70 has positive correlation with the expression of ASC-NLRP3, caspase-1, NF-κB and 4-hydroxynonenal and negative correlation with GSH:GSSG ratio. Conclusions The modulating effect of luteolin on the expression of HSP70, NF-κB and thereby on ASC-NLRP3 complex may be claimed for its pancreato-protective activity.

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Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1

Pharmacological Research ◽

10.1016/j.phrs.2019.104348 ◽

2019 ◽

Vol 147 ◽

pp. 104348 ◽

Cited By ~ 6

Author(s):

Jiasi Wu ◽

Yu Luo ◽

Qing Jiang ◽

Sheng Li ◽

Wenge Huang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammasome Activation ◽

Coptis Chinensis ◽

Caspase 1 ◽

Nlrp3 Inflammasome Activation

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The Essential Oil of Artemisia argyi H.Lév. and Vaniot Attenuates NLRP3 Inflammasome Activation in THP-1 Cells

Frontiers in Pharmacology ◽

10.3389/fphar.2021.712907 ◽

2021 ◽

Vol 12 ◽

Author(s):

Pengxiao Chen ◽

Qi Bai ◽

Yanting Wu ◽

Qiongzhen Zeng ◽

Xiaowei Song ◽

...

Keyword(s):

Essential Oil ◽

Nlrp3 Inflammasome ◽

Therapeutic Potential ◽

Inflammasome Activation ◽

Caspase 1 ◽

Artemisia Argyi ◽

Nlrp3 Inflammasome Activation ◽

Long Time

Artemisia argyi H. Lév. and Vaniot is a traditional medical herb that has been used for a long time in China and other Asian counties. Essential oil is the main active fraction of Artemisia argyi H. Lév. and Vaniot, and its anti-inflammatory potential has been observed in vitro and in vivo. Here, we found that the essential oil of Artemisia argyi H. Lév. and Vaniot (EOAA) inhibited monosodium urate (MSU)- and nigericin-induced NLRP3 inflammasome activation. EOAA suppressed caspase-1 and IL-1β processing and pyroptosis. NF-κB p65 phosphorylation and translocation were also inhibited. In addition, EOAA suppressed nigericin-induced NLRP3 inflammasome activation without blocking ASC oligomerization, suggesting that it may inhibit NLRP3 inflammasome activation by preventing caspase-1 processing. Our study thus indicates that EOAA inhibits NLRP3 inflammasome activation and has therapeutic potential against NLRP3-driven diseases.

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Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity

Blood Advances ◽

10.1182/bloodadvances.2020003918 ◽

2021 ◽

Vol 5 (5) ◽

pp. 1523-1534

Author(s):

Johan Courjon ◽

Océane Dufies ◽

Alexandre Robert ◽

Laurent Bailly ◽

Cédric Torre ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Myeloid Cells ◽

Inflammasome Activation ◽

Caspase 1 ◽

Molecular Pattern ◽

Nlrp3 Inflammasome Activation ◽

Healthy Donors ◽

Activation Potential ◽

Key Factor ◽

Pathogen Associated Molecular Pattern

Abstract Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

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Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats

Bioscience Reports ◽

10.1042/bsr20180892 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 12

Author(s):

Bin Zheng ◽

Shuncai Zhang ◽

Yanlu Ying ◽

Xinying Guo ◽

Hengchang Li ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Nlrp3 Inflammasome ◽

Caspase 1 ◽

Pyrin Domain ◽

Improvement Effect ◽

Improved Performance ◽

Inflammasome Activity ◽

Adrenergic Receptor Agonist ◽

Nlrp3 Activity

The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist that inhibits the activation of NLRP3. Thus, it was hypothesized that Dex could attenuate TBI by inhibiting NLRP3 inflammasome activity in hippocampus. Rats were subjected to controlled cortical impact method to induce TBI, and treated with Dex. The effect of Dex treatment on the cognitive function, NLRP3 activity, and microglial activation in rat brain tissues was assessed. The administration of Dex improved performance of TBI rats in Morris water maze (MWM) test, which was associated with the increased neurone viability and suppressed microglia activity. Moreover, the administration of Dex inhibited the neuroinflammation in brain tissue as well as the expressions of NLRP3 and caspase-1. Additionally, Dex and NLRP3 inhibitor, BAY-11-7082 had a synergistic effect in inhibiting NLRP3/caspase-1 axis activity and improving TBI. The findings outlined in the current study indicated that the improvement effect of Dex on TBI was related to its effect on NLRP3 activity.

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