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

Perla Villani Borges, Katelim Hottz Moret, Raghavendra Nulgumnalli Manjunathaiah, 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...
September 15, 2016: 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...
April 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...
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...
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
Kyung-Ah Cho, Peter B Kang
Impaired lipid metabolism and inflammatory pathways have individually been implicated in the development of insulin resistance in skeletal muscle; however, little evidence is available to date linking the two in this context. In this study, we explored a potential molecular mechanism underlying insulin resistance in myoblasts mediated by the crosstalk between lipid accumulation and inflammatory pathways. We examined the influence of perilipin 2 (PLIN2), one of the most highly expressed lipid droplet-associated proteins in skeletal muscle, on glucose uptake and on the nucleotide‑binding domain, leucine‑rich repeat containing protein 3 (NLRP3) inflammasome in vitro...
September 2015: International Journal of Molecular Medicine
Matthew G Frank, Linda R Watkins, Steven F Maier
PURPOSE OF REVIEW: Glucocorticoids have been universally regarded as anti-inflammatory; however, a considerable number of studies now demonstrate that under some conditions, glucocorticoids are capable of potentiating neuroinflammatory processes (i.e. priming), a permissive function of glucocorticoids. The present review addresses recent evidence that provides insight into the mechanism(s) of glucocorticoid-induced neuroinflammatory priming. RECENT FINDINGS: Glucocorticoids have been found to prime inflammasomes [i...
August 2015: Current Opinion in Endocrinology, Diabetes, and Obesity
Irma Garcia-Martinez, Mohamed E Shaker, Wajahat Z Mehal
SIGNIFICANCE: Sterile inflammation is a common finding present in various metabolic disorders. This type of inflammation is mediated by damage-associated molecular patterns (DAMPs) that are released upon cellular injury to activate pattern recognition receptors on innate immune cells and amplify organ damage. RECENT ADVANCES: In the last decade, DAMPs, such as high-mobility group protein B1, nucleic acids (DNA, RNA), adenosine triphosphate, and other metabolites, were found to contribute to the inflammatory response in diabetes, gout, obesity, steatohepatitis, and atherosclerosis...
December 10, 2015: Antioxidants & Redox Signaling
Yang Zhou, Deming Zhao, Ruichao Yue, Sher Hayat Khan, Syed Zahid Ali Shah, Xiaomin Yin, Lifeng Yang, Zhongqiu Zhang, Xiangmei Zhou
Mycobacterium bovis is the causative agent of tuberculosis in cattle. Infection of macrophages with M. bovis leads to the activation of the "nucleotide binding and oligomerization, leucine-rich repeat and pyrin domains-containing protein 3" (NLRP3) and "absent in melanoma 2" (AIM2) inflammasomes, which in turn triggers release of the proinflammatory cytokine interleukin-1β (IL-1β) that contributes to bacterial clearance and plays a crucial role in the host defense. However, NLRP3 and AIM2 inflammasome activation is influenced by several factors and how IL-1β secretion by M...
July 2015: Antonie Van Leeuwenhoek
Wei Ye, Yingfeng Lei, Mengmeng Yu, Yongni Xu, Mengyuan Cao, Lan Yu, Liang Zhang, Puyuan Li, Wentao Bai, Zhikai Xu, Fanglin Zhang
Persistent high fever is one typical clinical symptom of hemorrhagic fever with renal syndrome (HFRS) and circulating interleukin-1β (IL-1β) is elevated throughout HFRS. The mechanisms responsible for viral induction of IL-1β secretion are unknown. In the present study, Hantaan virus (HTNV) induced the secretion of IL-1β in the human monocytic cell line THP-1. Induction of IL-1β by HTNV relies on the activation of caspase-1. Small hairpin RNA knockdown in HTNV-infected THP-1 cells indicated that nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) recruits the adaptor apoptosis-associated speck-like protein and caspase-1 to form an NLRP3 inflammasome complex, crucial for the induction of IL-1β...
June 2015: International Journal of Molecular Medicine
Yunfei Chi, Jiake Chai, Chengfeng Xu, Hongmin Luo, Qinxue Zhang
BACKGROUND: Hyperglycemia with insulin resistance remains a challenging problem in severely burned patients. Recent studies indicated the involvement of the nucleotide-binding domain and the leucine-rich, repeat-containing family, pyrin-containing 3 (NLRP3) inflammasome in insulin resistance and a beneficial role of apelin in insulin resistance. Our aim was to investigate whether apelin inhibits the activation of the NLRP3 inflammasome and ameliorates insulin resistance in severely burned rats...
June 2015: Surgery
Kairui Mao, Shuzhen Chen, Yan Wang, Yan Zeng, Yonglei Ma, Yu Hu, Hong Zhang, Shuhui Sun, Xiaodong Wu, Guangxun Meng, Gang Pei, Bing Sun
Inflammasomes are multiprotein complexes that trigger the activation of caspase-1 and the maturation of IL-1β, which are critical for inflammation and control of pathogen infection. Although the function of inflammasomes in immune response and disease development is well studied, the molecular mechanism by which inflammasomes are activated and assembled remains largely unknown. In this study, we found that β-arrestin1, a key regulator of the G protein-coupled receptor signaling pathway, was required for nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasome-mediated IL-1β production and caspase-1 activation, but it had no effect on absent in melanoma 2 (AIM2) inflammasome activation...
February 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Michael D Weber, Matthew G Frank, Kevin J Tracey, Linda R Watkins, Steven F Maier
Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo...
January 7, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Francisco Ortiz, Darío Acuña-Castroviejo, Carolina Doerrier, José C Dayoub, Luis C López, Carmen Venegas, José A García, Ana López, Huayqui Volt, Marta Luna-Sánchez, Germaine Escames
Mucositis is a common and distressing side effect of chemotherapy or radiotherapy that has potentially severe consequences, and no treatment is available. The purpose of this study was to analyze the molecular pathways involved in the development of oral mucositis and to evaluate whether melatonin can prevent this pathology. The tongue of male Wistar rats was subjected to irradiation (X-ray YXLON Y.Tu 320-D03 irradiator; the animals received a dose of 7.5 Gy/day for 5 days). Rats were treated with 45 mg/day melatonin or vehicle for 21 days postirradiation, either by local application into their mouths (melatonin gel) or by subcutaneous injection...
January 2015: Journal of Pineal Research
Hyo-Yeon Kim, Seok-Joo Kim, Sun-Mee Lee
Inflammasome activation by danger signals in ischemia/reperfusion (I/R) injury is responsible for the sterile inflammatory response. Signals triggering formation and activation of the inflammasome involve the generation of oxidative stress. The aim of this study was to examine the molecular mechanisms of inflammasome activation and the involvement of reactive oxygen species in hepatic I/R. I/R induced the formation of nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes and the subsequent serum release of interleukin 1β...
January 2015: FEBS Journal
Han Wei, Chao Hu, Jinbo Xie, Chao Yang, Yue Zhao, Yaqi Guo, Zhinan Mei, Lvyi Chen, Zhou Lan
Our previous study demonstrates that Dolichos falcata Klein (DF) ameliorates the gouty arthritis induced by monosodium urate (MSU) crystals, and one of the active components, doliroside A, contributed to the anti-gouty arthritis effect of DF according to the in vitro study. However, there is still little known about the potential beneficial effects and possible mechanism of action of doliroside A on gouty arthritis. Here, we investigated the underlying mechanism of action of doliroside A in vitro and the anti-inflammatory effects of doliroside A in vivo...
October 5, 2014: European Journal of Pharmacology
Sandhya Ganesan, Vijay A K Rathinam, Lukas Bossaller, Kelly Army, William J Kaiser, Edward S Mocarski, Christopher P Dillon, Douglas R Green, Tanya N Mayadas, Stuart M Levitz, Amy G Hise, Neal Silverman, Katherine A Fitzgerald
Inflammasomes are central mediators of host defense to a wide range of microbial pathogens. The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in triggering caspase-1-dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-Glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells. In this study, we sought to determine the contribution of β-glucans to C...
September 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
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