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nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)

Fawaz Awad, Eman Assrawi, Claire Jumeau, Sophie Georgin-Lavialle, Laetitia Cobret, Philippe Duquesnoy, William Piterboth, Lucie Thomas, Katia Stankovic-Stojanovic, Camille Louvrier, Irina Giurgea, Gilles Grateau, Serge Amselem, Sonia-Athina Karabina
Inflammasomes are multiprotein complexes nucleating around an NLR (Nucleotide-binding domain and Leucine-rich Repeat containing protein), which regulate the secretion of the pro-inflammatory interleukin (IL)-1β and IL-18 cytokines. Monocytes and macrophages, the main cells expressing the inflammasome genes, adapt to their surrounding microenvironment by a phenotypic polarization towards a pro-inflammatory M1 phenotype that promotes inflammation or an anti-inflammatory M2 phenotype important for resolution of inflammation...
2017: PloS One
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
Sirpa Loukovaara, Niina Piippo, Kati Kinnunen, Maria Hytti, Kai Kaarniranta, Anu Kauppinen
PURPOSE: Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro-inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR)...
March 8, 2017: Acta Ophthalmologica
Xiuju Dai, Mikiko Tohyama, Masamoto Murakami, Koji Sayama
Skin epidermis, in addition to its barrier function, is able to actively sense harmful pathogens using pattern recognition receptors. In immune cells, the nucleotide-binding oligomerization domain, leucine-rich repeat, pyrin domain containing 3 (NLRP3) inflammasome can mediate innate immunity against viral infection via a mechanism involving viral dsRNA recognition. Epidermal keratinocytes express NLRP3 inflammasome, which can sense contact sensitizers and mite allergens, leading to pro-interleukin (IL)-1β and pro-IL-18 cleavage into their active forms...
March 7, 2017: Experimental Dermatology
Zhijuan Mao, Chanchan Liu, Suqiong Ji, Qingmei Yang, Hongxiang Ye, Haiyan Han, Zheng Xue
The etiology and pathogenesis of Parkinson's disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days...
February 28, 2017: Neurochemical Research
Zhenning Liu, Xiaokai Wang, Yu Wang, Min Zhao
Paraquat can result in dysfunction of multiple organs after ingestion in human. However, the mechanisms of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome activation in acute kidney injury have not been clearly demonstrated. The aim of this study was to determine the effect of NLRP3 inflammasome activation and its regulation by nuclear factor-kappa B (NF-κB) and death-associated protein kinase (DAPK). Male Wistar rats were treated with intraperitoneal injection of paraquat at 20 mg/kg, and NF-κB inhibitor BAY 11-7082 was pretreated at 10 mg/kg 1 h before paraquat exposure...
February 18, 2017: Immunologic Research
Carolina Pellegrini, Luca Antonioli, Gloria Lopez-Castejon, Corrado Blandizzi, Matteo Fornai
Several lines of evidence point out the relevance of nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome as a pivotal player in regulating the integrity of intestinal homeostasis and shaping innate immune responses during bowel inflammation. Intensive research efforts are being made to achieve an integrated view about the protective/detrimental role of canonical and non-canonical NLRP3 inflammasome activation in the maintenance of intestinal microenvironment integrity...
2017: Frontiers in Immunology
Liangkun Pan, Nan Hang, Chao Zhang, Yu Chen, Shuchun Li, Yang Sun, Zhongjun Li, Xiangbao Meng
A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family,pyrin domain-containing 3,also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated...
January 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mark R Zielinski, Dmitry Gerashchenko, Svetlana A Karpova, Varun Konanki, Robert W McCarley, Fayyaz S Sutterwala, Robert E Strecker, Radhika Basheer
Both sleep loss and pathogens can enhance brain inflammation, sleep, and sleep intensity as indicated by electroencephalogram delta (δ) power. The pro-inflammatory cytokine interleukin-1 beta (IL-1β) is increased in the cortex after sleep deprivation (SD) and in response to the Gram-negative bacterial cell-wall component lipopolysaccharide (LPS), although the exact mechanisms governing these effects are unknown. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome protein complex forms in response to changes in the local environment and, in turn, activates caspase-1 to convert IL-1β into its active form...
May 2017: Brain, Behavior, and Immunity
Yukio Fujiwara, Yoshiyuki Hizukuri, Kyoko Yamashiro, Naoyuki Makita, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara, Yasuhiro Hayashi
Macrophage activation is the main immunological process occurring during the development of several diseases, and the heterogeneity of macrophage activation or differentiation has been suggested to be involved in disease progression. In the present study, we attempted to identify molecules specifically expressed on human classically activated macrophages (M1) to investigate the significance of the M1-like phenotype in human diseases. Human monocyte-derived macrophages were differentiated into M1, M2a, M2b and M2c phenotypes, and also M1(-) (the M1 phenotype differentiated with interferon-γ) to eliminate the strong effects of lipopolysaccharides (LPS) on the gene expression profile...
November 2016: Clinical & Translational Immunology
Abdurrahman Dolunay, Sefika Pinar Senol, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Bahar Tunctan
The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3), an intracellular signaling molecule that senses many environmental- and pathogen/host-derived factors, has been implicated in the pathogenesis of several diseases associated with inflammation. It has been suggested that NLRP3 inflammasome inhibitors may have a therapeutic potential in the treatment of NLRP3-related inflammatory diseases. The aim of this study was to determine whether inhibition of NLRP3 inflammasome prevents inflammatory hyperalgesia induced by lipopolysaccharide (LPS) in mice as well as changes in expression/activity of nuclear factor κB (NF-κB), caspase-1/11, nicotinamide adenine dinucleotide phosphate oxidase (NOX), and endothelial/neuronal/inducible nitric oxide synthase (eNOS/nNOS/iNOS) that may regulate NLRP3/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/pro-caspase-1 inflammasome formation and activity by using a selective NLRP3 inflammasome inhibitor, MCC950...
April 2017: Inflammation
W L Lu, D Z Song, J L Yue, T T Wang, X D Zhou, P Zhang, L Zhang, D M Huang
AIM: To explore the role of NLRP3 (NACHT [nucleotide-binding oligomerization], LRR [leucine-rich repeat] and PYD [pyrin domain] domains-containing protein 3) inflammasome in the inflammatory response of human periodontal ligament fibroblasts (HPDLFs). METHODOLOGY: The expression of NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) in inflammatory periapical tissues and HPDLFs was examined by immunohistochemical and immunofluorescent staining...
November 19, 2016: International Endodontic Journal
Perla Villani Borges, Katelim Hottz Moret, Nulgumnalli Manjunathaiah Raghavendra, Thadeu Estevam Maramaldo Costa, Ana Paula Monteiro, Alan Brito Carneiro, Patrícia Pacheco, Jairo Ramos Temerozo, Dumith Chequer Bou-Habib, Maria das Graças Henriques, Carmen Penido
Activation of toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) triggers an innate immune response, via cytokine production and inflammasome activation. Herein, we have investigated the modulatory effect of the natural limonoid gedunin on TLR activation in vitro and in vivo. Intraperitoneal (i.p.) pre- and post-treatments of C57BL/6 mouse with gedunin impaired the influx of mononuclear cells, eosinophils and neutrophils, as well as the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide (NO), triggered by lipopolysaccharide (LPS) in mouse pleura...
January 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ping Ke, Bo-Zong Shao, Zhe-Qi Xu, Wei Wei, Bin-Ze Han, Xiong-Wen Chen, Ding-Feng Su, Chong Liu
Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1)...
2016: PloS One
Ingar Olsen, Sim K Singhrao
Inflammasomes are responsible for the maturation of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-18, and IL-33 and activation of inflammatory cell death, pyroptosis. They assemble in response to cellular infection and stress or to tissue damage, promote inflammatory reactions, and are important in regulating innate immunity particularly by acting as platforms for activation of caspase proteases. They appear to be involved in several pathological processes activated by microbes including Alzheimer's disease (AD)...
June 15, 2016: Journal of Alzheimer's Disease: JAD
Ejiofor A D Ezekwe, Chengyu Weng, Joseph A Duncan
The Staphylococcus aureus toxin, α-hemolysin, is an important and well-studied virulence factor in staphylococcal infection. It is a soluble monomeric protein that, once secreted by the bacterium, forms a heptameric pore in the membrane of a broad range of host cell types. Hemolysin was recently discovered to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial and endothelial cells, ADAM10 activation is required for the toxin's activity against these cells. In host monocytic cells, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of pro-inflammatory cytokines and cell death...
March 30, 2016: Toxins
Yujuan Wang, Jakub W Hanus, Mones S Abu-Asab, Defen Shen, Alexander Ogilvy, Jingxing Ou, Xi K Chu, Guangpu Shi, Wei Li, Shusheng Wang, Chi-Chao Chan
Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis...
January 8, 2016: International Journal of Molecular Sciences
Changyun Hu, Heyuan Ding, Yangyang Li, James A Pearson, Xiaojun Zhang, Richard A Flavell, F Susan Wong, Li Wen
Studies in animal models and human subjects have shown that both innate and adaptive immunity contribute to the pathogenesis of type 1 diabetes (T1D). Whereas the role of TLR signaling pathways in T1D has been extensively studied, the contribution of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein (NLRP) 3 inflammasome pathway remains to be explored. In this study, we report that NLRP3 plays an important role in the development of T1D in the nonobese diabetic (NOD) mouse model...
September 8, 2015: Proceedings of the National Academy of Sciences of the United States of America
Wei Chi, Hongrui Chen, Fei Li, Yingting Zhu, Wei Yin, Yehong Zhuo
BACKGROUND: Acute glaucoma is a significantly sight-threatening cause of irreversible blindness in the world characterized by a sudden and substantial intraocular pressure (IOP) increase and subsequent retinal ganglion cell (RGC) death. This study aims to explore the role of high-mobility group box 1 (HMGB1) in an acute glaucoma mouse model. METHODS: An acute glaucoma model was induced by a rapid and substantial increase IOP to 70 mmHg for 60 min via anterior chamber punctured and affused with Balance Salt Solution in C57BL/6 mice...
July 30, 2015: Journal of Neuroinflammation
Rosa Lavieri, Anna Rubartelli, Sonia Carta
The cell stress and redox responses are increasingly acknowledged as factors contributing to the generation and development of the inflammatory response. Several inflammation-inducing stressors have been identified, inside and outside of the cell. Furthermore, many hereditary diseases associate with inflammation and oxidative stress, suggesting a role for mutated proteins as stressors. The nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is an important node at the crossroad between redox response and inflammation...
January 2016: Journal of Leukocyte Biology
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