scholarly journals Involvement of HO-1 and Autophagy in the Protective Effect of Magnolol in Hepatic Steatosis-Induced NLRP3 Inflammasome Activation In Vivo and In Vitro

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 924
Author(s):  
Ni-Chun Kuo ◽  
Shieh-Yang Huang ◽  
Chien-Yi Yang ◽  
Hsin-Hsueh Shen ◽  
Yen-Mei Lee
Keyword(s):  
Hepatic Steatosis ◽  
Nlrp3 Inflammasome ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Heme Oxygenase 1 ◽  
Autophagic Flux ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nlrp3 Inflammasome Activation ◽  
Wide Range

Magnolol (MG) is the main active compound of Magnolia officinalis and exerts a wide range of biological activities. In this study, we investigated the effects of MG using tyloxapol (Tylo)-induced (200 mg/kg, i.p.) hyperlipidemia in rats and palmitic acid (PA)-stimulated (0.3 mM) HepG2 cells. Our results showed that Tylo injection significantly increased plasma levels of triglyceride and cholesterol as well as superoxide anion in the livers, whereas MG pretreatment reversed these changes. MG reduced hepatic lipogenesis by attenuating sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) proteins and Srebp-1, Fas, Acc, and Cd36 mRNA expression as well as upregulated the lipolysis-associated genes Hsl, Mgl, and Atgl. Furthermore, MG reduced plasma interleukin-1β (IL-1β) and protein expression of NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and caspase 1 as well as upregulated nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and induction of heme oxygenase-1 (HO-1) in hepatocytes of Tylo-treated rats. Enhanced autophagic flux by elevation of autophagy related protein 5-12 (ATG5-12), ATG7, Beclin1, and microtubule-associated protein light chain 3 B II (LC3BII)/LC3BI ratio, and reduction of sequestosome-1 (SQSTM1/p62) and phosphorylation of mTOR was observed by MG administration. However, autophagy inhibition with 3-methyladenine (3-MA) in HepG2 cells drastically abrogated the MG-mediated suppression of inflammation and lipid metabolism. In conclusion, MG inhibited hepatic steatosis-induced NLRP3 inflammasome activation through the restoration of autophagy to promote HO-1 signaling capable of ameliorating oxidative stress and inflammatory responses.

scholarly journals The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110181
Author(s):  
Rongrong Bai ◽  
Yue Lang ◽  
Jie Shao ◽  
Yu Deng ◽  
Reyisha Refuhati ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Purinergic Receptor ◽  
Cerebrovascular Diseases ◽  
New Drugs ◽  
Signalling Pathways ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nlrp3 Inflammasome Activation ◽  
Pathological Mechanism

Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex and a vital component of the immune system. Emerging evidence has indicated that the NLRP3 inflammasome plays an important role in cerebrovascular diseases. The function of the NLRP3 inflammasome in the pathogenesis of cerebrovascular diseases remains an interesting field of research. In this review, we first summarised the pathological mechanism of cerebrovascular diseases and the pathological mechanism of the NLRP3 inflammasome in aggravating atherosclerosis and cerebrovascular diseases. Second, we outlined signalling pathways through which the NLRP3 inflammasome participates in aggravating or mitigating cerebrovascular diseases. Reactive oxygen species (ROS)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ROS/thioredoxin-interacting protein (TXNIP) and purinergic receptor-7 (P2X7R) signalling pathways can activate the NLRP3 inflammasome; activation of the NLRP3 inflammasome can aggravate cerebrovascular diseases by mediating apoptosis and pyroptosis. Autophagy/mitochondrial autophagy, nuclear factor E2-related factor-2 (Nrf2), interferon (IFN)-β, sirtuin (SIRT), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) reportedly alleviate cerebrovascular diseases by inhibiting NLRP3 inflammasome activation. Finally, we explored specific inhibitors of the NLRP3 inflammasome based on the two-step activation of the NLRP3 inflammasome, which can be developed as new drugs to treat cerebrovascular diseases.

scholarly journals A Synthetic Small Molecule F240B Decreases NLRP3 Inflammasome Activation by Autophagy Induction

2020 ◽  
Vol 11 ◽  
Author(s):  
Chun-Hsien Wu ◽  
Chin Heng Gan ◽  
Lan-Hui Li ◽  
Jen-Che Chang ◽  
Shin-Tai Chen ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Membrane Integrity ◽  
Mechanistic Study ◽  
Autophagic Flux ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Inflammatory Agent ◽  
Nlrp3 Inflammasome Activation ◽  
Autophagy Induction ◽  
Anti Inflammatory

Conjugated polyenes are a class of widely occurring natural products with various biological functions. We previously identified 4-hydroxy auxarconjugatin B (4-HAB) as anti‐inflammatory agent with an IC50 of ~20 µM. In this study, we synthesized a new anti‐inflammatory 4-HAB analogue, F240B, which has an IC50 of less than 1 µM. F240B dose-dependently induced autophagy by increasing autophagic flux, LC3 speck formation and acidic vesicular organelle formation. F240B inhibited NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome activation through autophagy induction. In a mechanistic study, F240B inhibited interleukin (IL)-1β (IL-1β) precursor expression, promoted degradation of NLRP3 and IL-1β, and reduced mitochondrial membrane integrity loss in an autophagy-dependent manner. Additionally, F240B inhibited apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and speck formation without affecting the interaction between NLRP3 and ASC or NIMA-related kinase 7 (NEK7) and double-stranded RNA-dependent kinase (PKR). Furthermore, F240B exerted in vivo anti-inflammatory activity by reducing the intraperitoneal influx of neutrophils and the levels of IL-1β, active caspase-1, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in lavage fluids in a mouse model of uric acid crystal-induced peritonitis. In conclusion, F240B attenuated the NLRP3 inflammasome through autophagy induction and can be developed as an anti-inflammatory agent in the future.

Increasing Autophagy ameliorate all-trans-retinal-activated NLRP3 Inflammasome 2 in human THP-1 macrophage cells

2021 ◽  
Author(s):  
Qingqing Xia ◽  
Lvxing Huang ◽  
Hengyi Chen ◽  
Yingying Zhou ◽  
Lingmin Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Cell Counting ◽  
Autophagic Flux ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Related Proteins ◽  
Excessive Activation ◽  
Insight Into

Abstract BackgroundProfound inflammation that mediated by innate immune sensors can be observed in retina, and is considered to play an important role in the pathogenesis of all-trans-retinal (atRAL)-caused retinal degeneration. However, the underlying mechanism remains elusive. MethodsCell viability was detected with Cell Counting Kit-8 (CCK-8). The concentration of IL-1β was evaluated using IL-1β ELISA Kits. The levels of autophagy-related proteins were measured by Western blotting. The measurement of autophagic flux was performed with virus vectors packing tandem monomeric mCherry-eGFP-tagged LC3B. ResultsWe focused on studying the effects of atRAL on macrophage cell line THP-1 and determining the underlying signal pathway through pharmacological and genetical manipulation. We first found the maturation and release of IL-1β was regulated by the activation of NLRP3 inflammasome. We secondly found that mitochondria-associated reactive oxygen species (ROS) were involved in the regulation of NLRP3 inflammasome activation and caspase 1 cleavage. Finally, we found that atRAL functionally activated autophagy in THP-1 cells, and atRAL-caused NLRP3 inflammasome activation is suppressed by autophagy. Overall, our results show atRAL simultaneously activates NLRP3 inflammasome and autophagy in THP-1 cells, and increasing autophagy leads to the inhibition of the excessive activation of NLRP3 inflammasome. Our study provides new insight into the pathogenesis of aging related retina degeneration.

Targeting heme oxygenase-1 by quercetin ameliorates alcohol-induced acute liver injury via inhibiting NLRP3 inflammasome activation

2018 ◽  
Vol 9 (8) ◽  
pp. 4184-4193 ◽  
Author(s):  
Shu Liu ◽  
Lei Tian ◽  
Guangrui Chai ◽  
Bo Wen ◽  
Bingyuan Wang
Keyword(s):  
Liver Injury ◽  
Heme Oxygenase ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Heme Oxygenase 1 ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

Quercetin can ameliorate alcohol-induced acute liver injury via inducing heme oxygenase-1 and inhibiting NLRP3 inflammasome activation.

Microparticles released as a consequence of lipid-induced toxicity promote NLRP3 inflammasome activation in HepG2 cells

2014 ◽  
Vol 46 ◽  
pp. e1
Author(s):  
C. Paternostro ◽  
E. Benetti ◽  
S. Cannito ◽  
E. Novo ◽  
F. Chiazza ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Hepg2 Cells ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Ahmad Alatshan ◽  
Szilvia Benkő
Keyword(s):  
Immune Responses ◽  
Nuclear Receptors ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Inflammatory Conditions ◽  
Physiological Processes ◽  
Nlrp3 Inflammasome Activation ◽  
Wide Range ◽  
Multiple Levels ◽  
Approved Drugs

Nuclear receptors are important bridges between lipid signaling molecules and transcription responses. Beside their role in several developmental and physiological processes, many of these receptors have been shown to regulate and determine the fate of immune cells, and the outcome of immune responses under physiological and pathological conditions. While NLRP3 inflammasome is assumed as key regulator for innate and adaptive immune responses, and has been associated with various pathological events, the precise impact of the nuclear receptors on the function of inflammasome is hardly investigated. A wide variety of factors and conditions have been identified as modulators of NLRP3 inflammasome activation, and at the same time, many of the nuclear receptors are known to regulate, and interact with these factors, including cellular metabolism and various signaling pathways. Nuclear receptors are in the focus of many researches, as these receptors are easy to manipulate by lipid soluble molecules. Importantly, nuclear receptors mediate regulatory mechanisms at multiple levels: not only at transcription level, but also in the cytosol via non-genomic effects. Their importance is also reflected by the numerous approved drugs that have been developed in the past decade to specifically target nuclear receptors subtypes. Researches aiming to delineate mechanisms that regulate NLRP3 inflammasome activation draw a wide range of attention due to their unquestionable importance in infectious and sterile inflammatory conditions. In this review, we provide an overview of current reports and knowledge about NLRP3 inflammasome regulation from the perspective of nuclear receptors, in order to bring new insight to the potentially therapeutic aspect in targeting NLRP3 inflammasome and NLRP3 inflammasome-associated diseases.

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