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NOD- like receptor protein 3 (NLRP3 ) inflammasomes and interleukin-1beta (IL-1beta)

Mingkuan Chen, Yue Xing, Ailing Lu, Wei Fang, Bing Sun, Changbin Chen, Wanqing Liao, Guangxun Meng
Cryptococcus neoformans is an opportunistic fungal pathogen that causes cryptococcosis in immunocompromised patients as well as immunocompetent individuals. Host cell surface receptors that recognize C. neoformans have been widely studied. However, intracellular sensing of this pathogen is still poorly understood. Our previous studies have demonstrated that both biofilm and acapsular mutant of C. neoformans are able to activate the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome. In the current study, it was found that opsonization-mediated internalization of encapsulated C...
November 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Qian Li, Xiong Zhang, Weicheng Wang, LeLe Li, Qiang Xu, Xudong Wu, Yanhong Gu
CPT-11 is widely used for cancer therapy as a chemotherapeutic agent. Despite its good efficacy, a large number of side effects appeared during decades of clinical application. Delayed diarrhea, at dose limiting toxicity, happens after 24h of treatment and the rate of occurrence is up to 90%. Although many investments have been made on this negative impact, the real molecular mechanism of delayed diarrhea is poorly understood. In this study, we have discovered that CPT-11 promotes macrophage infiltration into intestinal tissues and activates the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, resulting in a robust IL-1β response and colonic inflammation similar to DSS (dextran sodium sulfate) induced experimental colitis...
December 1, 2015: Toxicology and Applied Pharmacology
Letteria Minutoli, Pietro Antonuccio, Natasha Irrera, Mariagrazia Rinaldi, Alessandra Bitto, Herbert Marini, Gabriele Pizzino, Carmelo Romeo, Antonina Pisani, Giuseppe Santoro, Domenico Puzzolo, Carlo Magno, Francesco Squadrito, Antonio Micali, Domenica Altavilla
We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) in wild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 1 and 7 days of reperfusion or a sham TI/R. Furthermore, two groups of WT mice were treated at the beginning of reperfusion and up to 7 days with two inflammasome inhibitors, BAY 11-7082 (20 mg/kg i...
December 2015: Journal of Pharmacology and Experimental Therapeutics
Gregory M Orlowski, Jeff D Colbert, Shruti Sharma, Matthew Bogyo, Stephanie A Robertson, Kenneth L Rock
Sterile particles induce robust inflammatory responses that underlie the pathogenesis of diseases like silicosis, gout, and atherosclerosis. A key cytokine mediating this response is IL-1β. The generation of bioactive IL-1β by sterile particles is mediated by the NOD-like receptor containing a pyrin domain 3 (NLRP3) inflammasome, although exactly how this occurs is incompletely resolved. Prior studies have found that the cathepsin B inhibitor, Ca074Me, suppresses this response, supporting a model whereby ingested particles disrupt lysosomes and release cathepsin B into the cytosol, somehow activating NLRP3...
August 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Jing Xiong, Yang Wang, Ning Shao, Pao Gao, Hui Tang, Hua Su, Chun Zhang, Xian-Fang Meng
BACKGROUND/AIMS: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. METHODS: Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them...
2015: Kidney & Blood Pressure Research
Thomas Gicquel, Sacha Robert, Pascal Loyer, Tatiana Victoni, Aude Bodin, Catherine Ribault, Florence Gleonnec, Isabelle Couillin, Elisabeth Boichot, Vincent Lagente
The Nod-like receptor family protein 3 (NLRP3)-inflammasome pathway is known to be activated by danger signals such as monosodium urate (MSU). We investigated the role of P2 purinergic receptors in the activation of NLRP3-inflammasome pathway after MSU treatment of primary human monocyte-derived macrophages (MDMs). After initial stimulation with a low concentration of LPS (0.1 µg/ml), a 6 h treatment with MSU crystals (250, 500, and 1000 µg/ml) induced the MDMs to release IL-1β, IL-1α, and IL-6 in a dose-dependent manner...
October 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Woo-Chang Cheong, Hye-Ri Kang, Hyunyee Yoon, Suk-Jo Kang, Jenny P-Y Ting, Moon Jung Song
The inflammasome is a molecular platform that stimulates the activation of caspase-1 and the processing of pro-interleukin (IL)-1β and pro-IL-18 for secretion. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is activated by diverse molecules and pathogens, leading to the formation of the NLRP3 inflammasome. Recent studies showed that the NLRP3 inflammasome mediates innate immunity against influenza A virus (IAV) infection. In this study, we investigated the function of the IAV non-structural protein 1 (NS1) in the modulation of NLRP3 inflammasome...
2015: PloS One
Xue-Yang Deng, Hong-Yan Li, Jun-Jun Chen, Rui-Peng Li, Rong Qu, Qiang Fu, Shi-Ping Ma
Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm...
September 15, 2015: Behavioural Brain Research
Qilin Liu, Jianwei Li
Diabetes has become a global epidemic disease now. Its chronic progressive deterioration and the acuteand chronic complications affect the quality of the patients' lives seriously. The prevention and treatment of diabetes has become one of the research focuses in recent years. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome can recognize the metabolic stress signals, and cause caspase-1 activation and interleukin-lp (IL-1p) production, and is closely related to diabetes development...
December 2014: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
Ji-Won Han, Do-Wan Shim, Woo-Young Shin, Kang-Hyuk Heo, Su-Bin Kwak, Eun-Jeong Sim, Jae-Hyun Jeong, Tae-Bong Kang, Kwang-Ho Lee
Emodin, an active constituent of oriental herbs, is widely used to treat allergy, inflammation, and other symptoms. This study provides the scientific basis for the anti-inflammasome effects of emodin on both in vitro and in vivo experimental models. Bone marrow-derived macrophages were used to study the effects of emodin on inflammasome activation by using inflammasome inducers such as ATP, nigericin, and silica crystals. The lipopolysaccharide (LPS)-induced endotoxin shock model was employed to study the effect of emodin on in vivo efficacy...
April 10, 2015: International Journal of Molecular Sciences
Jessica Queen, Shivani Agarwal, Jazel S Dolores, Christian Stehlik, Karla J F Satchell
Activation of inflammasomes is an important aspect of innate immune responses to bacterial infection. Recent studies have linked Vibrio cholerae secreted toxins to inflammasome activation by using murine macrophages. To increase relevance to human infection, studies of inflammasome-dependent cytokine secretion were conducted with the human THP-1 monocytic cell line and corroborated in primary human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical strains of V. cholerae activated ASC (apoptosis-associated speck-like protein-containing a CARD domain)-dependent release of interleukin-1β (IL-1β) when cultured with human THP-1 cells, but the pattern of induction was distinct, depending on the repertoire of toxins the strains produced...
June 2015: Infection and Immunity
Rebecca C Coll, Avril A B Robertson, Jae Jin Chae, Sarah C Higgins, Raúl Muñoz-Planillo, Marco C Inserra, Irina Vetter, Lara S Dungan, Brian G Monks, Andrea Stutz, Daniel E Croker, Mark S Butler, Moritz Haneklaus, Caroline E Sutton, Gabriel Núñez, Eicke Latz, Daniel L Kastner, Kingston H G Mills, Seth L Masters, Kate Schroder, Matthew A Cooper, Luke A J O'Neill
The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations...
March 2015: Nature Medicine
Mausita Karmakar, Michael Katsnelson, Hesham A Malak, Neil G Greene, Scott J Howell, Amy G Hise, Andrew Camilli, Aras Kadioglu, George R Dubyak, Eric Pearlman
Although neutrophils are the most abundant cells in acute infection and inflammation, relatively little attention has been paid to their role in inflammasome formation and IL-1β processing. In the present study, we investigated the mechanism by which neutrophils process IL-1β in response to Streptococcus pneumoniae. Using a murine model of S. pneumoniae corneal infection, we demonstrated a requirement for IL-1β in bacterial clearance, and we showed that Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1 are essential for IL-1β production and bacterial killing in the cornea...
February 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Yasser A Aldhamen, Yuliya Pepelyayeva, David P W Rastall, Sergey S Seregin, Efthalia Zervoudi, Despoina Koumantou, Charles F Aylsworth, Dionisia Quiroga, Sarah Godbehere, Dimitris Georgiadis, Efstratios Stratikos, Andrea Amalfitano
Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression...
2015: Journal of Innate Immunity
Yu-Li Cheng, Li-Qiong Song, Yuan-Ming Huang, Yan-Wen Xiong, Xiao-Ai Zhang, Hui Sun, Xin-Ping Zhu, Guang-Xun Meng, Jian-Guo Xu, Zhi-Hong Ren
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection in humans can cause acute haemorrhagic colitis and severe haemolytic uraemic syndrome. The role of enterohaemolysin (Ehx) in the pathogenesis of O157:H7-mediated disease in humans remains undefined. Recent studies have revealed the importance of the inflammatory response in O157:H7 pathogenesis in humans. We previously reported that Ehx markedly induced interleukin-1β (IL-1β) production in human macrophages. Here, we investigated the disparity in Ehx-induced IL-1β production between human and mouse macrophages and explored the underlying mechanism regarding the activation of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasomes...
June 2015: Immunology
Ming-Xing Wang, Yang-Liu Liu, Ying Yang, Dong-Mei Zhang, Ling-Dong Kong
Nuciferine, a major aporphine alkaloid of the leaves of Nelumbo nucifera, was found to decrease serum urate levels and improved kidney function, as well as inhibited system and renal interleukin-1β (IL-1β) secretion in potassium oxonate-induced hyperuricemic mice. Furthermore, nuciferine reversed expression alteration of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette, subfamily G, membrane 2 (ABCG2), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), and organic cation/carnitine transporters 1/2 (OCTN1/2) in hyperuricemic mice...
January 15, 2015: European Journal of Pharmacology
Bo-Zong Shao, Wei Wei, Ping Ke, Zhe-Qi Xu, Jv-Xiang Zhou, Chong Liu
AIMS: Activation of cannabinoid receptor 2 (CB2R) has been reported to ameliorate the pathogenesis of experimental autoimmune encephalomyelitis (EAE). In this study, we examined whether autophagy is involved in the beneficial effect of CB2R on EAE and explored the mechanism with a focus on inflammasome activation. METHODS: EAE severity was analyzed with clinical score and histological score stained by hematoxylin and eosin or luxol fast blue in spinal cord. Immunoblot analysis was conducted to detect proteins of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-related caspase-1 (Casp-1) and the maturation of interleukin (IL)-1β as well as autophagy-related light chain 3 (LC3), and Beciln 1 both in vivo and in vitro...
December 2014: CNS Neuroscience & Therapeutics
C Paget, M T Chow, N A Gherardin, P A Beavis, A P Uldrich, H Duret, M Hassane, F Souza-Fonseca-Guimaraes, D A Mogilenko, D Staumont-Sallé, N K Escalante, G R Hill, P Neeson, D S Ritchie, D Dombrowicz, T Mallevaey, F Trottein, G T Belz, D I Godfrey, M J Smyth
Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3(bright) γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3(bright) γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1(+) T-cell receptor...
February 2015: Immunology and Cell Biology
Yetiş Gültekin, Elif Eren, Nesrin Özören
The novel nucleotide oligomerization domain (NOD)-like receptor (NLR) with a caspase activation and recruitment domain (CARD) 3 (NLRC3) protein belongs to the NLR family of cytosolic pathogen recognition receptors. NLRC3 has the characteristic NOD and leucine-rich repeat configuration with a less well defined CARD. T lymphocytes are known to have high NLRC3 expression, which may be involved in suppression of T cell activation. Here, we report that NLRC3 is a cytoplasmic protein that negatively regulates pro-IL-1β maturation...
2015: Journal of Innate Immunity
Patrick M Giguère, Bryan J Gall, Ejiofor A D Ezekwe, Geneviève Laroche, Brian K Buckley, Chahnaz Kebaier, Justin E Wilson, Jenny P Ting, David P Siderovski, Joseph A Duncan
Inflammasomes are multi-protein complexes that regulate maturation of the interleukin 1β-related cytokines IL-1β and IL-18 through activation of the cysteine proteinase caspase-1. NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is a key component of inflammasomes that assemble in response to a wide variety of endogenous and pathogen-derived danger signals. Activation of the NLRP3-inflammasome and subsequent secretion of IL-1β is highly regulated by at least three processes: transcriptional activation of both NLRP3 and pro-IL-1β genes, non-transcriptional priming of NLRP3, and final activation of NLRP3...
November 28, 2014: Journal of Biological Chemistry
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