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NLRP3 inflammasome

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https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#1
Yue Wang, Zhihua Han, Yuqi Fan, Junfeng Zhang, Kan Chen, Lin Gao, Huasu Zeng, Jiatian Cao, Changqian Wang
BACKGROUND/AIMS: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. METHODS: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models...
March 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28326544/personalized-genetics-of-the-cholinergic-blockade-of-neuroinflammation
#2
REVIEW
Alon Simchovitz, Michael T Heneka, Hermona Soreq
Acetylcholine signaling is essential for cognitive functioning and blocks inflammation. To maintain homeostasis, cholinergic signaling is subjected to multi-leveled and bidirectional regulation by both proteins and non-coding microRNAs ('CholinomiRs'). CholinomiRs coordinate the cognitive and inflammatory aspects of cholinergic signaling by targeting major cholinergic transcripts including the acetylcholine hydrolyzing enzyme acetylcholinesterase (AChE). Notably, AChE inhibitors are the only currently approved line of treatment for Alzheimer's disease patients...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28326454/quercetin-and-ascorbic-acid-suppress-fructose-induced-nlrp3-inflammasome-activation-by-blocking-intracellular-shuttling-of-txnip-in-human-macrophage-cell-lines
#3
Jung-Yoon Choe, Seong-Kyu Kim
The aim of this study was to identify the role of thioredoxin-interacting protein (TXNIP) and its interaction with antioxidants in the activation of the fructose-induced NOD-like receptor protein 3 (NLRP3) inflammasome in human macrophages. The study was performed with U937 and THP-1 macrophage cell lines. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1β (IL-1β), IL-18, NLRP3, TXNIP, and caspase-1 protein expression was detected using western blotting. Quantitative real-time polymerase chain reaction was used to detect IL-1β, IL-18, and caspase-1 gene expression...
March 22, 2017: Inflammation
https://www.readbyqxmd.com/read/28322865/palmitic-acid-elicits-hepatic-stellate-cell-activation-through-inflammasomes-and-hedgehog-signaling
#4
Na-Na Duan, Xue-Jing Liu, Jian Wu
AIMS: Activation of hepatic stellate cells (HSCs) plays a pivotal role at the center of the fibrogenic progression in nonalcoholic steatohepatitis (NASH). However, it is poorly understood that how various molecules interact within HSCs during the progression of NASH to fibrosis. The aim of the present study is to delineate how inflammasome molecules, hedgehog signaling and autophagy provoke HSC activation using palmitic acid (PA) as a major insult. MAIN METHODS: Inflammasome activation, hedgehog signaling activity and autophagy in PA-exposed HSCs were determined to investigate their role in activation of human and rodent HSC lines or primary HSCs...
March 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28321151/the-antimalarial-chloroquine-suppresses-lps-induced-nlrp3-inflammasome-activation-and-confers-protection-against-murine-endotoxic-shock
#5
Xiaoli Chen, Ning Wang, Yuanfeng Zhu, Yongling Lu, Xin Liu, Jiang Zheng
Activation of the NLRP3 inflammasome, which catalyzes maturation of proinflammatory cytokines like IL-1β and IL-18, is implicated and essentially involved in many kinds of inflammatory disorders. Chloroquine (CQ) is a traditional antimalarial drug and also possesses an anti-inflammatory property. In this study, we investigated whether CQ suppresses NLRP3 inflammasome activation and thereby confers protection against murine endotoxic shock. CQ attenuated NF-κB and MAPK activation and prohibited expression of IL-1β, IL-18, and Nlrp3 in LPS treated murine bone marrow-derived macrophages (BMDMs), demonstrating its inhibitory effect on the priming signal of NLRP3 activation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28320833/inflammatory-changes-in-bone-marrow-microenvironment-associated-with-declining-b-lymphopoiesis
#6
Domenick E Kennedy, Katherine L Knight
B lymphopoiesis arrests precipitously in rabbits such that by 2-4 mo of age, before sexual maturity, little to no B lymphopoiesis occurs in the bone marrow (BM). Previously, we showed that in mice, adipocytes inhibit B lymphopoiesis in vitro by inducing inflammatory myeloid cells, which produce IL-1β. In this study, we characterized rabbit BM after the arrest of B lymphopoiesis and found a dramatic increase in fat, increased CD11b(+) myeloid cells, and upregulated expression of the inflammatory molecules, IL-1β and S100A9, by the myeloid cells...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320097/asiatic-acid-ameliorates-pulmonary-fibrosis-induced-by-bleomycin-blm-via-suppressing-pro-fibrotic-and-inflammatory-signaling-pathways
#7
Shu-Hong Dong, Yan-Wei Liu, Feng Wei, Hui-Zhen Tan, Zhi-Dong Han
Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice...
March 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320049/d-%C3%AE-hydroxybutyrate-promotes-functional-recovery-and-relieves-pain-hypersensitivity-in-mice-with-spinal-cord-injury
#8
Jiao Qian, Wenjun Zhu, Ming Lu, Bin Ni, Jun Yang
BACKGROUND AND PURPOSE: Spinal cord injury (SCI) leads to severe motor and sensory dysfunction and significantly reduces the quality of life. The aim of present work was to investigate the effect of administration of exogenous D-β-hydroxybutyrate (DBHB) on functional recovery and neuropathic pain in spinal-cord-injured mice. EXPERIMENTAL APPROACH: Mice were given a moderate-severe thoracic spinal contusion injury at the T9-10 level, and treated with exogenous DBHB...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28318352/the-role-of-nlrp3-casp1-in-inflammasome-mediated-neuroinflammation-and-autophagy-dysfunction-in-manganese-induced-hippocampal-dependent-impairment-of-learning-and-memory-ability
#9
Diya Wang, Jianbin Zhang, Wenkai Jiang, Zipeng Cao, Fang Zhao, Tongjian Cai, Michael Aschner, Wenjing Luo
Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood...
February 27, 2017: Autophagy
https://www.readbyqxmd.com/read/28318046/hepatitis-c-virus-induced-ccl5-secretion-from-macrophages-activates-hepatic-stellate-cells
#10
Reina Sasaki, Pradip B Devhare, Robert Steele, Ranjit Ray, Ratna B Ray
Hepatitis C virus (HCV) mediated chronic liver disease is a serious health problem around the world, and often causes fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). The mechanism of liver disease progression during HCV infection is still unclear, although inflammation is believed to be an important player in disease pathogenesis. We previously reported that macrophages including Kupffer cells exposed to HCV induce proinflammatory cytokines. These secreted cytokines may activate hepatic stellate cells (HSCs) towards fibrosis...
March 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28306139/the-tir-bb-loop-mimetic-as-1-prevents-nonalcoholic-steatohepatitis-and-hepatic-insulin-resistance-by-inhibiting-nlrp3-asc-inflammasome-activation
#11
Xiaolu Wang, Yun Gao, Juan Song, Chao Tang, Man Wang, Linli Que, Li Liu, Guoqing Zhu, Qi Chen, Yong Yao, Yong Xu, Jiantao Li, Yuehua Li
BACKGROUND AND PURPOSE: Non-alcoholic steatohepatitis (NASH) is characterized by excessive intracellular lipid accumulation, inflammation and hepatic insulin resistance. Considering the rising prevalence of NASH worldwide, it is urgent to find novel interventional approaches. The pro-inflammatory cytokine IL-1β, generated and released from the Kupffer cells, is considered to be an initiating event in NASH. AS-1, a synthetic low-molecule mimetic to myeloid differentiation primary response gene 88 (MyD88), has been reported to disrupt the IL-1R-MyD88 interaction...
March 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28303894/an-excessive-increase-in-glutamate-contributes-to-glucose-toxicity-in-%C3%AE-cells-via-activation-of-pancreatic-nmda-receptors-in-rodent-diabetes
#12
Xiao-Ting Huang, Chen Li, Xiang-Ping Peng, Jia Guo, Shao-Jie Yue, Wei Liu, Fei-Yan Zhao, Jian-Zhong Han, Yan-Hong Huang, Yang-Li, Qing-Mei Cheng, Zhi-Guang Zhou, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302726/the-rna-binding-protein-tristetraprolin-ttp-is-a-critical-negative-regulator-of-the-nlrp3-inflammasome
#13
Moritz Haneklaus, John D O'Neil, Andrew R Clark, Seth L Masters, Luke A J O'Neill
The NLRP3 inflammasome is a central regulator of inflammation in many common diseases, including atherosclerosis and Type 2 diabetes, driving the production of pro-inflammatory mediators such as IL-1β and IL-18. Due to its function as an inflammatory gatekeeper, expression and activation of NLRP3 need to be tightly regulated. In this study, we highlight novel post-transcriptional mechanisms that can modulate NLRP3 expression. We have identified the RNA-binding protein Tristetraprolin (TTP) as a negative regulator of NLRP3 in human macrophages...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#14
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28300164/role-of-purinergic-signaling-in-experimental-pneumococcal-meningitis
#15
Marco Zierhut, Susanne Dyckhoff, Ilias Masouris, Matthias Klein, Sven Hammerschmidt, Hans-Walter Pfister, Korcan Ayata, Marco Idzko, Uwe Koedel
Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298525/the-induction-of-pro-il-1%C3%AE-by-lipopolysaccharide-requires-endogenous-prostaglandin-e2-production
#16
Zbigniew Zasłona, Eva M Pålsson-McDermott, Deepthi Menon, Moritz Haneklaus, Ewelina Flis, Hannah Prendeville, Sarah E Corcoran, Marc Peters-Golden, Luke A J O'Neill
PGE2 has been shown to increase the transcription of pro-IL-1β. However, recently it has been demonstrated that PGE2 can block the maturation of IL-1β by inhibiting the NLRP3 inflammasome in macrophages. These apparently conflicting results have led us to reexamine the effect of PGE2 on IL-1β production. We have found that in murine bone marrow-derived macrophages, PGE2 via the cAMP/protein kinase A pathway is potently inducing IL-1β transcription, as well as boosting the ability of LPS to induce IL-1β mRNA and pro-IL-1β while inhibiting the production of TNF-α...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28297677/recombinant-bcg-expressing-esx-1-of-mycobacterium-marinum-combines-low-virulence-with-cytosolic-immune-signaling-and-improved-tb-protection
#17
Matthias I Gröschel, Fadel Sayes, Sung Jae Shin, Wafa Frigui, Alexandre Pawlik, Mickael Orgeur, Robin Canetti, Nadine Honoré, Roxane Simeone, Tjip S van der Werf, Wilbert Bitter, Sang-Nae Cho, Laleh Majlessi, Roland Brosch
Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacterium bovis BCG, provides limited protection. A feature of BCG is the partial deletion of the ESX-1 type VII secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked to increased immune signaling...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28293932/effect-of-tio%C3%A2-nanoparticles-on-inflammasome-mediated-airway-inflammation-and-responsiveness
#18
Byeong Gon Kim, Pureun Haneul Lee, Sun Hye Lee, Moo Kyun Park, An Soo Jang
PURPOSE: Nanoparticles (NPs) may cause cell and tissue damage, leading to local and systemic inflammatory responses and adverse effects on health due to the inhalation of particulate matter. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (pro-IL-1β) into its mature form and may induce acute and chronic immune responses to NPs. However, little is known about the response of the inflammasome to NP exposure via the airways in asthma...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28289409/mitochondrial-dna-activates-the-nlrp3-inflammasome-and-predisposes-to-type-1-diabetes-in-murine-model
#19
Daniela Carlos, Frederico R C Costa, Camila A Pereira, Fernanda A Rocha, Juliana N U Yaochite, Gabriela G Oliveira, Fernando S Carneiro, Rita C Tostes, Simone G Ramos, Dario S Zamboni, Niels O S Camara, Bernhard Ryffel, João S Silva
Although a correlation between polymorphisms of NOD-like receptor family-pyrin domain containing 3 (NLRP3) and predisposition to type 1 diabetes (T1D) has been identified, the potential function and activation of the NLRP3 inflammasome in T1D have not been clarified. The present study shows that non-obese diabetic mice exhibited increased NLRP3, and pro-IL-1β gene expression in pancreatic lymph nodes (PLNs). Similar increases in gene expression of NLRP3, apoptosis associated speck like protein (ASC) and pro-IL-1β were induced by multiple low doses of streptozotocin (STZ) in C57BL/6 mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28288918/increased-carbon-dioxide-levels-stimulate-neutrophils-to-produce-microparticles-and-activate-the-nucleotide-binding-domain-like-receptor-3-inflammasome
#20
Stephen R Thom, Veena M Bhopale, JingPing Hu, Ming Yang
We hypothesized that elevations of carbon dioxide (CO2) commonly found in modern buildings will stimulate leukocytes to produce microparticles (MPs) and activate the nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome due to mitochondrial oxidative stress. Human and murine neutrophils generate MPs with high interleukin-1β (IL-1β) content when incubated ex vivo in buffer equilibrated with 0.1-0.4% additional CO2. Enhanced MPs production requires mitochondrial reactive oxygen species production, which is mediated by activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase...
March 10, 2017: Free Radical Biology & Medicine
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