scholarly journals Benzyl Isothiocyanate Reduces High-Fat/High-Cholesterol/Cholic Acid Diet-Induced Non-Alcoholic Steatohepatitis by Inhibiting the Activation of NLRP3 Inflammasome (P06-084-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Li-Li Ko ◽  
Haw-wen Chen ◽  
Chong-Kuei Lii
Keyword(s):  
Total Cholesterol ◽  
Cholic Acid ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
High Cholesterol ◽  
High Fat ◽  
Benzyl Isothiocyanate ◽  
Alcoholic Steatohepatitis ◽  
Caspase 1 ◽  
Acid Diet

Abstract Objectives Non-alcoholic steatohepatitis (NASH) is one kind of fatty liver disease, which is associated with obesity. Benzyl isothiocyanate (BITC), an organosulfur compound enriched in cruciferous vegetables, shows anti-inflammatory, antioxidant, and anti-tumor activities. This study examined whether BITC protects against high-fat/high-cholesterol/cholic acid diet-induced NASH and the underlying mechanisms involved. Methods Male C57BL/6 J mice were randomly assigned into three groups: normal diet (ND), high-fat/high-cholesterol/cholic acid diet (HFCCD), or HFCCD supplemented with 0.1% BITC. After a 9-weeks feeding, liver tissues and blood samples were collected for analysis. Results Compared with mice fed with ND, the liver weight and the contents of serum GOP, GPT, and total cholesterol as well as hepatic triglycerides and total cholesterol were significantly increased in mice fed with HFCCD (p < 0.05). HFCCD-induced increases in serum GPT and hepatic triglyceride were significantly decreased by BITC (p < 0.05). Histological examination revealed that macrophage infiltration, fibrosis, and the formation of crown-like structure were induced in mice fed with HFCCD, and these inductions were attenuated by BITC. Increases in the expression of NLRP3 mRNA and protein and caspase 1 and IL-1β mRNA as well as the cleaved caspase 1 (p20) and IL-1β (p17) proteins in the liver as well as serum IL-1β concentration were evidenced in HFCCD-fed mice. In the presence of BITC, HFCCD-induced hepatic NLRP3, caspase 1, and IL-1β expression was mitigated. Conclusions These findings suggest that BITC possesses potent anti-steatohepatitis activity, and this protection is likely to be associated with the inhibition of NLRP3 inflammasome activation. Funding Sources This study was supported by the Minister of Science and Technology, Taiwan.

scholarly journals NLRP3 Inflammasome Activation Controls Vascular Smooth Muscle Cells Phenotypic Switch in Atherosclerosis

2021 ◽  
Vol 23 (1) ◽  
pp. 340
Author(s):  
Fabienne Burger ◽  
Daniela Baptista ◽  
Aline Roth ◽  
Rafaela Fernandes da Silva ◽  
Fabrizio Montecucco ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Lineage Tracing ◽  
High Cholesterol Diet ◽  
Atherosclerotic Plaques ◽  
Inflammasome Activation ◽  
High Cholesterol ◽  
Phenotypic Switch ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Activated Monocytes

(1) Background: Monocytes and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome orchestrate lipid-driven amplification of vascular inflammation promoting the disruption of the fibrous cap. The components of the NLRP3 inflammasome are expressed in macrophages and foam cells within human carotid atherosclerotic plaques and VSMCs in hypertension. Whether monocytes and NLRP3 inflammasome activation are direct triggers of VSMC phenotypic switch and plaque disruption need to be investigated. (2) Methods: The direct effect of oxLDL-activated monocytes in VSMCs co-cultured system was demonstrated via flow cytometry, qPCR, ELISA, caspase 1, and pyroptosis assay. Aortic roots of VSMCs lineage tracing mice fed normal or high cholesterol diet and human atherosclerotic plaques were used for immunofluorescence quantification of NLRP3 inflammasome activation/VSMCs phenotypic switch. (3) Results: OxLDL-activated monocytes reduced α-SMA, SM22α, Oct-4, and upregulation of KLF-4 and macrophage markers MAC2, F4/80 and CD68 expression as well as caspase 1 activation, IL-1β secretion, and pyroptosis in VSMCs. Increased caspase 1 and IL-1β in phenotypically modified VSMCs was detected in the aortic roots of VSMCs lineage tracing mice fed high cholesterol diet and in human atherosclerotic plaques from carotid artery disease patients who experienced a stroke. (4) Conclusions: Taken together, these results provide evidence that monocyte promote VSMC phenotypic switch through VSMC NLRP3 inflammasome activation with a likely detrimental role in atherosclerotic plaque stability in human atherosclerosis.

Freshwater clam extract reduces liver injury by lowering cholesterol accumulation, improving dysregulated cholesterol synthesis and alleviating inflammation in high-fat, high-cholesterol and cholic acid diet-induced steatohepatitis in mice

2018 ◽  
Vol 9 (9) ◽  
pp. 4876-4887 ◽  
Author(s):  
Hsien-Tsung Yao ◽  
Pei-Feng Lee ◽  
Chong-Kuei Lii ◽  
Yun-Ta Liu ◽  
Szu-Han Chen
Keyword(s):  
Liver Injury ◽  
Cholic Acid ◽  
Cholesterol Synthesis ◽  
Corbicula Fluminea ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Freshwater Clam ◽  
Acid Diet ◽  
Protective Food

Freshwater clam (Corbicula fluminea) is a traditional liver-protective food in Asia.

scholarly journals Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome

2020 ◽  
Vol 21 (8) ◽  
pp. 2790 ◽  
Author(s):  
Gabsik Yang ◽  
Joo Hyeon Jang ◽  
Sung Wook Kim ◽  
Sin-Hee Han ◽  
Kyung-Ho Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Immune Cell ◽  
Inflammasome Activation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Caspase 1 ◽  
Triglyceride Accumulation ◽  
Nlrp3 Inflammasome Activation ◽  
Primary Mouse

Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms.

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

2013 ◽  
Vol 81 (8) ◽  
pp. 2997-3008 ◽  
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.

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

2019 ◽  
Vol 147 ◽  
pp. 104348 ◽  
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

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

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.

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

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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