Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation

The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.

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Bushen-Yizhi Formula Alleviates Neuroinflammation via Inhibiting NLRP3 Inflammasome Activation in a Mouse Model of Parkinson’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/3571604 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Yousheng Mo ◽

Erjin Xu ◽

Renrong Wei ◽

Baoluu Le ◽

Lei Song ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Neuronal Degeneration ◽

Interleukin 1 ◽

Inflammasome Activation ◽

Neuroprotective Effects ◽

Nlrp3 Inflammasome Activation

Parkinson’s disease (PD), the second most common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although the molecular mechanisms underlying dopaminergic neuronal degeneration in PD remain unclear, neuroinflammation is considered as the vital mediator in the pathogenesis and progression of PD. Bushen-Yizhi Formula (BSYZ), a traditional Chinese medicine, has been demonstrated to exert antineuroinflammation in our previous studies. However, it remains unclear whether BSYZ is effective for PD. Here, we sought to assess the neuroprotective effects and explore the underlying mechanisms of BSYZ in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine- (MPTP-) induced mouse model of PD. Our results indicate that BSYZ significantly alleviates the motor impairments and dopaminergic neuron degeneration of MPTP-treated mice. Furthermore, BSYZ remarkably attenuates microglia activation, inhibits NLPR3 activation, and decreases the levels of inflammatory cytokines in MPTP-induced mouse brain. Also, BSYZ inhibits NLRP3 activation and interleukin-1βproduction of the 1-methyl-4-phenyl-pyridinium (MPP+) stimulated BV-2 microglia cells. Taken together, our results indicate that BSYZ alleviates MPTP-induced neuroinflammation probably via inhibiting NLRP3 inflammasome activation in microglia. Collectively, BSYZ may be a potential therapeutic agent for PD and the related neurodegeneration diseases.

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Macrophage–NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

Neuroscience Bulletin ◽

10.1007/s12264-020-00544-0 ◽

2020 ◽

Vol 36 (9) ◽

pp. 1035-1045

Author(s):

Hong-Bin Lin ◽

Guan-Shan Wei ◽

Feng-Xian Li ◽

Wen-Jing Guo ◽

Pu Hong ◽

...

Keyword(s):

Ischemic Stroke ◽

Mouse Model ◽

Nlrp3 Inflammasome ◽

Cardiac Dysfunction ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation

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Epithelial Aryl Hydrocarbon Receptor Protects From Mucus Production by Inhibiting ROS-Triggered NLRP3 Inflammasome in Asthma

Frontiers in Immunology ◽

10.3389/fimmu.2021.767508 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xinyue Hu ◽

Yingchun Shen ◽

Yilin Zhao ◽

Ji Wang ◽

Xin Zhang ◽

...

Keyword(s):

Mouse Model ◽

Aryl Hydrocarbon Receptor ◽

Airway Inflammation ◽

Nlrp3 Inflammasome ◽

Allergic Airway Inflammation ◽

Ros Generation ◽

Inflammasome Activation ◽

Mucus Production ◽

Aryl Hydrocarbon ◽

Cockroach Allergen

BackgroundDespite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations.ObjectivesWe sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma.MethodsCockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated.ResultsCockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs.ConclusionsThese results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation.

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NLRP3 inflammasome activation in the thymus of MPTP-induced Parkinsonian mouse model

Toxicology Letters ◽

10.1016/j.toxlet.2018.02.003 ◽

2018 ◽

Vol 288 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Lu Wen ◽

Qiu-Shuang Zhang ◽

Yang Heng ◽

Ying Chen ◽

Shuo Wang ◽

...

Keyword(s):

Mouse Model ◽

Nlrp3 Inflammasome ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation

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β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer’s disease pathology

Journal of Neuroinflammation ◽

10.1186/s12974-020-01948-5 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Daniel C. Shippy ◽

Connor Wilhelm ◽

Patel A. Viharkumar ◽

Thomas J. Raife ◽

Tyler K. Ulland

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Nlrp3 Inflammasome ◽

Ketone Bodies ◽

Late Onset ◽

Inflammasome Activation ◽

Age Related ◽

Nlrp3 Inflammasome Activation ◽

5Xfad Mouse

Abstract Alzheimer’s disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, β-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD. Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.

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