The NLRP3 inflammasome drives inflammation in ischemia/reperfusion injury after transient middle cerebral artery occlusion in mice

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 92, P. 221 - 231

Published: Dec. 9, 2020

Cerebral ischemia induces a profound neuro-inflammatory response, but the underlying molecular mechanisms are poorly understood. Inflammasomes (NLRP1, NLRP3, NLRC4, AIM2) intracellular multi-protein complexes which can induce sets of pro-inflammatory cyto- and chemokines, thereby guide inflammation. We, here, assessed functional role NLRP3 in ischemia/reperfusion (I/R) injury mouse model transient cerebral ischemia.Ischemic stroke was induced C57Bl/6 mice by 60 min middle artery occlusion (tMCAO) 3, 7 or 23 h reperfusion, paradigm I/R injury. The expression patterns inflammasomes ischemic hemispheres were evaluated semiquantitative real-time PCR Western Blot analysis accompanied protein localization using immunocytochemistry. Finally, animals treated with inflammasome inhibitors Sulforaphane, Genipin, MCC950 vehicle, directly before upon recanalization after tMCAO. Stroke outcome assessed, including infarct size deficits, local inflammatory neuronal survival as well blood-brain barrier function on day 1 tMCAO.After tMCAO relative gene levels increased 20-30x within hemisphere translated into an neurons. Accordingly, NLRP3-modulator, Bruton's Tyrosine Kinase (BTK), NLRP3-inducible cytokine IL-1β significantly rose. Lesser non-significant changes seen for other inflammasomes. Application covering all specifically reduced volumes when given clear evidence activation caspase 1. This attenuating effect coincided less immune cell infiltration preservation integrity.Our data show that induction neurons drives neuroinflammation acute stroke. Early blockade protects from mitigating inflammation stabilizing barrier.

Language: Английский

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Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures

Journal of Neuroinflammation, Journal Year: 2019, Volume and Issue: 16(1)

Published: March 28, 2019

Microglia are important for secreting chemical mediators of inflammatory responses in the central nervous system. Interleukin (IL)-10 and IL-1β secreted by glial cells support neuronal functions, but related mechanisms remain vague. Our goal was to demonstrate efficacy IL-10 suppressing inflammasome activation mice with epileptic seizure based on an epileptic-seizure mouse model.In this study, which seizures were induced administering picrotoxin (PTX) used as a case group, injected saline employed control group. The expression nucleic acids, cytokines, or signaling pathways detected reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, Western blotting.Our results demonstrated that inhibits production through two distinct mechanisms: (1) Treatment lipopolysaccharides (LPS) overexpression microglia reduced NLRP3 activity, thus inhibiting caspase-1-related maturation; (2) next, autocrine found subsequently promote signal transducer activator transcription-3 (STAT-3), reducing amounts pro-IL-1β.Our indicate is potentially effective treatment inflammation encephalopathy, suggest potential usefulness treating autoimmune ailments.

Language: Английский

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Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: May 31, 2021

Abstract The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR inherent immune cell sensors. NLRP3 can detect tissue damage and pathogen invasion through innate sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation nuclear factor kappa B (NF-κB) pathways mitogen-activated protein kinase (MAPK) pathway, thus increasing transcription genes encoding proteins related to inflammasome. complex with multiple components, including an NAIP, CIITA, HET-E, TP1 (NACHT) domain; apoptosis-associated speck-like containing CARD (ASC); leucine-rich repeat (LRR) domain. After ischemic stroke, produce numerous proinflammatory cytokines, mediating nerve dysfunction brain edema ultimately leading death once activated. Ischemic stroke disease high rates mortality disability worldwide being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for clinical treatment stroke. Understanding may provide novel ideas approaches because targeting upstream downstream molecules pathway shows promise therapy. In this manuscript, we summarize existing evidence regarding composition inflammasome, involved inflammatory pathways, corresponding drugs or that exert effects after cerebral ischemia. This possible targets new

Language: Английский

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Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Dec. 13, 2018

Severe neuroinflammation is associated with blood brain barrier (BBB) disruption in CNS diseases. Although microglial activation and subsequent concentration changes cytokines/chemokines (C/Cs) are suggested to be key steps that worsen neuroinflammation, few data available concerning the significance of interaction microglia BBB cells this process. In study, we mimicked by adding LPS-activated (LPS-MG) abluminal side an vitro model composed endothelial (EC), pericytes (Peri) astrocytes (Ast). We then examined 27 C/Cs interactions between LPS-MG cells. caused collapse, as revealed decreases trans-endothelial electrical resistance (TEER) expression levels tight junction (TJ) proteins. Under these conditions, 19 were markedly increased on side. Unexpectedly, although alone released 10/19 C/Cs, their concentrations much lower than those detected supplemented LPS-MG. Co-culture Ast marked increases 12/19 while co-culture EC Peri resulted a significant increase 1/19 (fractalkine). These results suggest C/C dynamics breakdown not only activated but mainly due Ast.

Language: Английский

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Natural compounds flavonoids as modulators of inflammasomes in chronic diseases

International Immunopharmacology, Journal Year: 2020, Volume and Issue: 84, P. 106498 - 106498

Published: April 15, 2020

Language: Английский

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The beneficial therapeutic effects of plant‐derived natural products for the treatment of sarcopenia

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2022, Volume and Issue: 13(6), P. 2772 - 2790

Published: Aug. 12, 2022

Abstract Sarcopenia is an age‐related muscle disorder typically associated with a poor quality of life. Its definition has evolved over time, and several underlying causes sarcopenia in the elderly have been proposed. However, exact mechanisms involved sarcopenia, as well effective treatments for this condition, are not fully understood. The purpose article was to conduct comprehensive review previous evidence regarding definition, diagnosis, risk factors, efficacy plant‐derived natural products sarcopenia. methodological approach current narrative performed using PubMed, Scopus, Web Science databases, Google Scholar (up March 2021) order satisfy our objectives. substantial beneficial effects along safety some including curcumin, resveratrol, catechin, soy protein, ginseng on reported review. Based clinical studies, nutraceuticals functional foods may physical performance, handgrip knee‐extension strength, weight‐lifting capacity, time or distance travelled before feeling fatigued, mitochondrial function, fatigue, mean fibre area, total number myonuclei. In preclinical supplementation herbs bioactive compounds resulted increased plantaris mass, skeletal mass strength production, expression anabolic factors myogenin, Myf5 MyoD, enhanced inhibition atrophy We found that such nutritional status, inactivity, inflammation, oxidative stress, endocrine system dysfunction, insulin resistance, history chronic disease, mental health, genetic linked ginseng, without any significant side effects, Plant‐derived might effect various components Nevertheless, due limited human trials, benefits remain inconclusive. It suggested longitudinal studies better understand identifying treatment strategy based its pathophysiology, be undertaken future investigations.

Language: Английский

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Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer’s Disease Model <i>App</i>^{<i>NL-P-F</i>} Mice

Biological and Pharmaceutical Bulletin, Journal Year: 2025, Volume and Issue: 48(1), P. 75 - 79

Published: Jan. 30, 2025

Oxidative stress and neuroinflammation accompanied by microglial activation are increased in Alzheimer's disease (AD) contribute to the pathogenesis of AD. Nuclear factor erythroid-derived 2-related 2 (Nrf2) is a master transcription that acts as an endogenous defense mechanism against oxidative inflammation potential target for preventing Psoraleae Semen (PS) reportedly has antioxidant anti-inflammatory effects. This study aimed examine effects PS extract (PSE) on Nrf2 prevention cognitive dysfunction AppNL-P-F AD model mice. The PSE response element (ARE) activity cytoprotection PC12 cells BV-2 were evaluated. showed high ARE prevented 6-hydroxydopamine-induced cytotoxicity cells. Moreover, suppressed lipopolysaccharide-induced nitric oxide production Oral administration mice without affecting motor function. Our results support can development new preventive therapeutic agents focusing activation.

Language: Английский

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<p>Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340</p>

Drug Design Development and Therapy, Journal Year: 2019, Volume and Issue: Volume 13, P. 3465 - 3475

Published: Oct. 1, 2019

Background: Dexmedetomidine (Dex) was reported to exhibit anti-inflammatory effect in the nervous system. However, mechanism by which Dex exhibits anti-inflammation effects on LPS-stimulated BV2 microglia cells remains unclear. Thus, this study aimed investigate role of cells. Methods: The were stimulated lipopolysaccharides (LPS). infected with short-hairpin RNAs targeting NF-κB (NF-κB-shRNAs) and overexpression lentivirus, respectively. In addition, miR-340 mimics or inhibitor transfected into cells, Meanwhile, dual-luciferase reporter system assay used explore interaction CCK-8 detect viability Western blotting level levels TNF-α, IL-6, IL-1β, IL-2, IL-12, IL-10 MCP-1 measured ELISA. Results: significantly upregulated Dex-treated increased following infection lenti-NF-κB, markedly reversed Dex. LPS expression proinflammatory cytokines presence Moreover, enhanced via inhibiting cytokines. Furthermore, obviously inhibited LPS-induced phagocytosis Conclusion: Taken together, our results suggested that might exert upregulation miR-340. Therefore, serve as a potential agent for treatment neuroinflammation. Keywords: NF-κB, dexmedetomidine, postoperative cognitive dysfunction

Language: Английский

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Role of the NLRP3 Inflammasome: Insights Into Cancer Hallmarks

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 11

Published: Feb. 3, 2021

In response to a variety of stresses, mammalian cells activate the inflammasome for targeted caspase-dependent pyroptosis. The research community has recently begun deduce that activation is instigated by several known oncogenic stresses and metabolic perturbations; nevertheless, role inflammasomes in context cancer biology less understood. manipulating expression inflammasome, researchers have found NLRP3 serves as deterministic player conducting tumor fate decisions. Understanding mechanistic underpinning pro-tumorigenic anti-tumorigenic pathways might elucidate novel therapeutic onco-targets, thereby providing new opportunities manipulate augmenting activity prevent expansion achieve metastatic control. Accordingly, this review aims decode complexity NLRP3, whereby summarizing clustering findings into hallmarks tissue contexts may expedite consensus underscore potential drug translation.

Language: Английский

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Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(4), P. 632 - 632

Published: April 7, 2023

Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer's. Microglia are the brain's primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds anti-inflammatory antioxidant properties, epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related diseases involving activated microglia cells. The objective of current study was to examine molecular targets underlying effects EGCG in BV-2 cells were grown, stimulated, treated EGCG. Cytotoxicity nitric oxide (NO) production evaluated. Immunoassay, PCR array, WES™ Technology utilized evaluate inflammatory, neuroprotective modulators well signaling pathways involved mechanistic action neuroinflammation. Our findings showed that significantly inhibited mediator NO LPS-stimulated In addition, ELISA analysis revealed decreases cytokine IL-6 while it increases TNF-α. array downregulated MIF, CCL-2, CSF2. It also upregulated IL-3, IL-11, TNFS10. Furthermore, inflammatory mRNA expression mTOR, NF-κB2, STAT1, Akt3, CCL5, SMAD3 upregulating Ins2, Pld2, A20/TNFAIP3, GAB1. Additionally, reduced relative protein Akt3. These suggest be used its prevent diseases.

Language: Английский

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