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Inflammasome microglia

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https://www.readbyqxmd.com/read/28985759/role-of-microglial-amylin-receptors-in-mediating-beta-amyloid-a%C3%AE-induced-inflammation
#1
Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David MacTavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas
BACKGROUND: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer's disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors...
October 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28977782/edaravone-attenuates-the-proinflammatory-response-in-amyloid-%C3%AE-treated-microglia-by-inhibiting-nlrp3-inflammasome-mediated-il-1%C3%AE-secretion
#2
Hong-Mei Wang, Ting Zhang, Jian-Kang Huang, Jing-Yan Xiang, Jing-Jiong Chen, Jian-Liang Fu, Yu-Wu Zhao
BACKGROUND/AIMS: Microglial activation is an important pathological feature in the brains of patients with Alzheimer's disease (AD), and amyloid-β (Aβ) peptides play a crucial role in microglial activation. In addition, edaravone (EDA) was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1) mice. However, the mechanism by which EDA inhibits the Aβ-induced proinflammatory response in microglia is poorly understood. METHODS: The mitochondrial membrane potential (∆ψm) was evaluated using JC-1 staining...
October 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28941191/activating-%C3%AE-7-nicotinic-acetylcholine-receptor-inhibits-nlrp3-inflammasome-through-regulation-of-%C3%AE-arrestin-1
#3
Ping Ke, Bo-Zong Shao, Zhe-Qi Xu, Xiong-Wen Chen, Wei Wei, Chong Liu
AIMS: To evaluate whether activating α7 nicotinic acetylcholine receptor (α7nAChR) could inhibit the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of β-arrestin-1 in monocyte/macrophage system, thus contributing to the control of neuroinflammation. METHODS: The protein levels of NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1β (IL-1β) p17 and proIL-1β, IL-18 and proIL-18 were measured using Western blotting...
September 21, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28940479/activation-of-the-nlrp3-inflammasome-in-microglia-the-role-of-ceramide
#4
Hannah Scheiblich, Anna Schlütter, Douglas T Golenbock, Eicke Latz, Pilar Martinez-Martinez, Michael T Heneka
Inflammation within the CNS is a major component of many neurodegenerative diseases. A characteristic feature is the generation of microglia-derived factors that play an essential role in the immune response. IL-1β is a pro-inflammatory cytokine released by activated microglia, able to exacerbate injury at elevated levels. In the presence of caspase-1, pro-IL-1β is cleaved to the mature cytokine following NLRP3 inflammasome activation. Growing evidence suggests that ceramide plays a critical role in NLRP3 inflammasome assembly, however, the relationship between ceramide and inflammasome activation in microglia remains unknown...
September 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28903766/fluoxetine-enhanced-autophagy-ameliorates-early-brain-injury-via-inhibition-of-nlrp3-inflammasome-activation-following-subrachnoid-hemorrhage-in-rats
#5
Jian-Ru Li, Hang-Zhe Xu, Sheng Nie, Yu-Cong Peng, Lin-Feng Fan, Zhi-Jiang Wang, Cheng Wu, Feng Yan, Jing-Yin Chen, Chi Gu, Chun Wang, Jing-Sen Chen, Lin Wang, Gao Chen
BACKGROUND: The NLRP3 inflammasome is a multiprotein complex that regulates the innate immune inflammatory response by activating caspase-1 and subsequent IL-1β and IL-18. Fluoxetine has been shown to have the anti-inflammatory properties in many disease models. However, the effects and mechanisms of these effects of fluoxetine in early brain injury after subarachnoid hemorrhage (SAH) have not been defined. METHODS: The SAH model was induced by an endovascular perforation in adult male Sprague-Dawley (SD) rats weighing 300-320 g...
September 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28866823/neuroprotective-effects-of-baicalein-on-acrolein-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-of-rat-brain
#6
Wei-Zhong Zhao, Hsiang-Tsui Wang, Hui-Ju Huang, Yu-Li Lo, Anya Maan-Yuh Lin
Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson's disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation...
September 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28843178/esculentoside-a-exerts-anti-inflammatory-activity-in-microglial-cells
#7
Hui Yang, Yijian Chen, Linjie Yu, Yun Xu
Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. This study was designed to evaluate the pharmacological effects of EsA on lipopolysaccharide (LPS)-stimulated BV2 microglia and primary microglia cells. Our results indicated that EsA pretreatment significantly decreased LPS-induced production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) and impeded LPS-mediated upregulation of pro-inflammatory mediators' expression such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-a (TNF-α) in both BV2 microglia and primary microglia cells...
August 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28836226/the-ketone-body-%C3%AE-hydroxybutyrate-does-not-inhibit-synuclein-mediated-inflammasome-activation-in-microglia
#8
Vandana Deora, Eduardo A Albornoz, Kevin Zhu, Trent M Woodruff, Richard Gordon
Parkinson's disease (PD) is recognized as the most common neurodegenerative movement disorder and results in debilitating motor deficits. The accumulation and spread of neurotoxic synuclein aggregates in the form of Lewy bodies is a key pathological feature of PD. Chronic activation of the NLRP3 inflammasome by protein aggregates is emerging as a major pathogenic mechanism in progressive neurodegenerative disorders and is considered an important therapeutic target. Recently the ketone body, β-hydroxy butyrate (BHB), was shown to efficiently inhibit the NLRP3 inflammasome in macrophages, and in vivo models of inflammatory disease...
August 23, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28830026/progesterone-therapy-induces-an-m1-to-m2-switch-in-microglia-phenotype-and-suppresses-nlrp3-inflammasome-in-a-cuprizone-induced-demyelination-mouse-model
#9
Roya Aryanpour, Parichehr Pasbakhsh, Kazem Zibara, Zeinab Namjoo, Fatemeh Beigi Boroujeni, Saeed Shahbeigi, Iraj Ragerdi Kashani, Cordian Beyer, Adib Zendehdel
Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice...
August 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28821266/endogenous-hydrogen-sulphide-attenuates-nlrp3-inflammasome-mediated-neuroinflammation-by-suppressing-the-p2x7-receptor-after-intracerebral-haemorrhage-in-rats
#10
Hengli Zhao, Pengyu Pan, Yang Yang, Hongfei Ge, Weixiang Chen, Jie Qu, Jiantao Shi, Gaoyu Cui, Xin Liu, Hua Feng, Yujie Chen
BACKGROUND: Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown. METHODS: We employed a Sprague-Dawley rat of collagenase-induced ICH in the present study...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28798666/nlrp6-inflammasome-ameliorates-brain-injury-after-intracerebral-hemorrhage
#11
Peng-Fei Wang, Zhen-Guang Li, Yong Zhang, Xiao-Hua Ju, Xin-Wu Liu, Ai-Ming Zhou, Jing Chen
NLRP6 inflammasome, one of the important intracellular innate immune sensors, has been shown to regulate immune responses. However, its roles in the intracerebral hemorrhage (ICH) are completely not clear. In the present study, we investigated the expression profile and biological roles of NLRP6 inflammasome in perihematomal brain tissues of mice subjected to ICH. In this study, we investigated the expression profile of NLRP6 inflammasome in the perihematomal brain tissues and explored the biological role of NLRP6 inflammasome upon acute brain injury in mice subjected to ICH...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28655515/early-life-lipopolysaccharide-exposure-potentiates-forebrain-expression-of-nlrp3-inflammasome-proteins-and-anxiety-like-behavior-in-adolescent-rats
#12
Yuan Lei, Chu-Jun Chen, Xiao-Xin Yan, Zhiyuan Li, Xiao-Hua Deng
BACKGROUND: Neonatal inflammation may affect brain development and lead to cognitive and emotional deficits at adolescence and adulthood. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is the core component of NLRP3 inflammasome, which may involve in neuroinflammation. We explored if early-life exposure to the bacterial endotoxin lipopolysaccharide (LPS) could promote the expression of proteins related to NLRP3 inflammasome, including NLRP3, the apoptosis-associated speck-like protein (ASC) and cysteiny aspartate-specific protease (Caspase-1) in the forebrain and behavioral alteration in adolescent rats...
June 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28630327/virus-induced-inflammasome-activation-is-suppressed-by-prostaglandin-d2-dp1-signaling
#13
Rahul Vijay, Anthony R Fehr, Ann M Janowski, Jeremiah Athmer, Dorthea L Wheeler, Matthew Grunewald, Ramakrishna Sompallae, Samarchith P Kurup, David K Meyerholz, Fayyaz S Sutterwala, Shuh Narumiya, Stanley Perlman
Prostaglandin D2 (PGD2), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD2/DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b(+) cells in the CNS of infected mice...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#14
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28605578/roflupram-a-phosphodiesterase-4-inhibitior-suppresses-inflammasome-activation-through-autophagy-in-microglial-cells
#15
Tingting You, Yufang Cheng, Jiahong Zhong, Bingtian Bi, Bingqing Zeng, Wenhua Zheng, Haitao Wang, Jiangping Xu
Inhibition of phosphodiesterase 4 (PDE4) suppressed the inflammatory responses in the brain. However, the underlying mechanisms are poorly understood. Roflupram (ROF) is a novel PDE4 inhibitor. In the present study, we found that ROF enhanced the level of microtubule-associated protein 1 light chain 3 II (LC3-II) and decreased p62 in microglial BV-2 cells. Enhanced fluorescent signals were observed in BV-2 cells treated with ROF by Lysotracker red and acridine orange staining. In addition, immunofluorescence indicated a significant increase in punctate LC3...
August 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#16
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28595078/amyloidogenic-proteins-associated-with-neurodegenerative-diseases-activate-the-nlrp3-inflammasome
#17
REVIEW
Qian-Hang Shao, Xiao-Ling Zhang, Peng-Fei Yang, Yu-He Yuan, Nai-Hong Chen
Neuroinflammation has been shown as an essential factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and Multiple Sclerosis. Furthermore, activated microglia and increased pro-inflammatory cytokines are the major hallmarks in neurodegenerative diseases. A multimolecular complex named as inflammasome is involved in the process of inflammatory response, which can activate inflammatory caspases, leading to the cleavage and secretion of inflammatory cytokines, and finally generates a potent inflammatory response...
June 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#18
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28487495/naoling-decoction-restores-cognitive-function-by-inhibiting-the-neuroinflammatory-network-in-a-rat-model-of-alzheimer-s-disease
#19
Zian Xia, Weijun Peng, Shunhua Cheng, Bingwu Zhong, Chenxia Sheng, Chunhu Zhang, Wei Gong, Shuai Cheng, Jun Li, Zhe Wang
Neuroinflammation is central to the pathogenesis of Alzheimer's disease (AD). We previously showed that Naoling decoction (NLD), a traditional Chinese medicine, was effective against AD, acting by inhibiting expression of IL-1β and IL-6. In the present study, we generated the rat model of AD by injecting Aβ1-42 peptide intracerebroventricularly and evaluated the dose-dependent effects of NLD treatment. The NLD-treated rats exhibited significant improvements in cognitive function as evaluated by the Morris water maze test...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486969/activation-of-p2x7-receptor-and-nlrp3-inflammasome-assembly-in-hippocampal-glial-cells-mediates-chronic-stress-induced-depressive-like-behaviors
#20
Na Yue, Huijie Huang, Xiaocang Zhu, Qiuqin Han, Yalin Wang, Bing Li, Qiong Liu, Gencheng Wu, Yuqiu Zhang, Jin Yu
BACKGROUND: In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression...
May 10, 2017: Journal of Neuroinflammation
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