3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates NLRP3 inflammasome-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglial cells

Yang, Ji Woong; Yang, Seung-Ju; Na, Jung-Min; Hahn, Hoh‐Gyu; Cho, Sung‐Woo

doi:10.1016/j.bbrc.2017.10.131

Cited by 16 publications

(13 citation statements)

References 34 publications

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“…IL-1β is a critical proinflammatory cytokine, which subsequently enhances the production of both TNF-α and IL-6 [ 30 ] and promotes the generation of reactive oxygen species by microglia causing severe tissue and organ damage [ 20 ]. To investigate whether corylin affects the production of IL-1β by LPS-activated murine microglial cells, BV2 cells were pre-treated with various concentrations of corylin for 1 h, and then treated with LPS (1 μg/mL) for 48 h. The production of IL-1β was analyzed by ELISA.…”

Section: Resultsmentioning

confidence: 99%

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Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia

Huang

Wang

et al. 2018

BMC Complement Altern Med

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BackgroundInflammation has been found to be associated with many neurodegenerative diseases, including Parkinson’s and dementia. Attenuation of microglia-induced inflammation is a strategy that impedes the progression of neurodegenerative diseases.MethodsWe used lipopolysaccharide (LPS) to simulate murine microglia cells (BV2 cells) as an experimental model to mimic the inflammatory environment in the brain. In addition, we examined the anti-inflammatory ability of corylin, a main compound isolated from Psoralea corylifolia L. that is commonly used in Chinese herbal medicine. The production of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess reaction. The secretion of proinflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by LPS-activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, IL-1β and mitogen-activated protein kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot.ResultsOur experimental results demonstrated that corylin suppressed the production of NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the activation of caspase-1 and IL-1β by LPS-activated BV2 cells.ConclusionOur results indicate the anti-inflammatory effects of corylin acted through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in LPS-activated BV2 cells. These results suggest that corylin might have potential in treating brain inflammation and attenuating the progression of neurodegeneration diseases.

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Section: Resultsmentioning

confidence: 99%

“…The secretion of IL-1β augments inflammation and neurotoxicity, while leading to neurodegeneration and neuronal death. Thus, the inhibition of NLRP3 inflammasome is considered a therapeutic target of neurodegenerative diseases [ 17 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia

Huang

Wang

et al. 2018

BMC Complement Altern Med

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“…It is clear that the P2X7 receptor can modulate the neuroinflammation induced by LPS, once P2X7 receptor blockade may reduce inflammatory mediators release ( Bianco et al, 2006 ; Choi et al, 2007 ; Monif et al, 2009 ; He et al, 2017 ; Yang et al, 2018 ). Some works showed that LPS enhanced P2X7 receptor expression ( Choi et al, 2007 ; Yang et al, 2018 ), whereas other studies reported downregulation of P2X7 receptor expression ( Bianco et al, 2006 ; He et al, 2017 ). Similarly to the LPS-induced effects, P2X7 receptor overexpression was sufficient to trigger microglial activation in primary microglia derived from hippocampus ( Monif et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

The P2X7 Receptor: Central Hub of Brain Diseases

Andrejew

Oliveira-Giacomelli

Ribeiro

et al. 2020

Front. Mol. Neurosci.

112

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The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the extracellular milieu. The P2X7 receptor is widely expressed in the CNS, such as frontal cortex, hippocampus, amygdala and striatum, regions involved in neurodegenerative diseases and psychiatric disorders. Despite P2X7 receptor functions in glial cells have been extensively studied, the existence and roles of this receptor in neurons are still controversially discussed. Regardless, P2X7 receptors mediate several processes observed in neuropsychiatric disorders and brain tumors, such as activation of neuroinflammatory response, stimulation of glutamate release and neuroplasticity impairment. Moreover, P2X7 receptor gene polymorphisms have been associated to depression, and isoforms of P2X7 receptors are implicated in neuropsychiatric diseases. In view of that, the P2X7 receptor has been proposed to be a potential target for therapeutic intervention in brain diseases. This review discusses the molecular mechanisms underlying P2X7 receptor-mediated signaling in neurodegenerative diseases, psychiatric disorders, and brain tumors. In addition, it highlights the recent advances in the development of P2X7 receptor antagonists that are able of penetrating the central nervous system.

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“…This distinctive one-step pathway of inflammasome activation is typically seen in monocytes and have been recently seen in recent studies using BV2 cells ( Carta et al, 2011 ; Huang M.Y. et al, 2018 ; Yang et al, 2018 ).…”

Section: Resultsmentioning

confidence: 52%

Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease

Tayara

Espinosa-Oliva

García-Domínguez

et al. 2018

Front. Cell. Neurosci.

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The oral antidiabetic drug metformin is known to exhibit anti-inflammatory properties through activation of AMP kinase, thus protecting various brain tissues as cortical neurons, for example. However, the effect of metformin on the substantia nigra (SN), the main structure affected in Parkinson’s disease (PD), has not yet been studied in depth. Inflammation is a key feature of PD and it may play a central role in the neurodegeneration that takes place in this disorder. The aim of this work was to determine the effect of metformin on the microglial activation of the SN of rats using the animal model of PD based on the injection of the pro-inflammogen lipopolysaccharide (LPS). In vivo and in vitro experiments were conducted to study the activation of microglia at both the cellular and molecular levels. Our results indicate that metformin overall inhibits microglia activation measured by OX-6 (MHCII marker), IKKβ (pro-inflammatory marker) and arginase (anti-inflammatory marker) immunoreactivity. In addition, qPCR experiments reveal that metformin treatment minimizes the expression levels of several pro- and anti-inflammatory cytokines. Mechanistically, the drug decreases the phosphorylated forms of mitogen-activated protein kinases (MAPKs) as well as ROS generation through the inhibition of the NADPH oxidase enzyme. However, metformin treatment fails to protect the dopaminergic neurons of SN in response to intranigral LPS. These findings suggest that metformin could have both beneficial and harmful pharmacological effects and raise the question about the potential use of metformin for the prevention and treatment of PD.

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3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates NLRP3 inflammasome-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglial cells

Cited by 16 publications

References 34 publications

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia

The P2X7 Receptor: Central Hub of Brain Diseases

Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease

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