The Experts below are selected from a list of 9030 Experts worldwide ranked by ideXlab platform
Kwokfai So - One of the best experts on this subject based on the ideXlab platform.
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lycium barbarum polysaccharide attenuates alcoholic cellular injury through txnip nlrp3 inflammasome pathway
International Journal of Biological Macromolecules, 2014Co-Authors: Feiyue Xing, Jia Xiao, George L. Tipoe, Kwokfai SoAbstract:Abstract Lycium barbarum has been used as a traditional Chinese medicine to nourish liver, kidneys and the eyes. However, the underlying mechanisms of its hepatic-protective properties remain uncertain. In this study, we aimed to investigate whether thioredoxin-interacting protein (TXNIP) and NOD-like Receptor 3 (NLRP3) inflammasome mediated the attenuation of ethanol-induced hepatic injury by Lycium barbarum polysaccharide (LBP). Rat normal hepatocyte line BRL-3A was pre-treated with LBP prior to ethanol incubation. Hepatic damages, including apoptosis, inflammation, and oxidative stress, were measured. Then the inhibition of endogenous TXNIP expression was achieved by using its specific siRNA to test its possible involvement in the injury attenuation. We found that 50 μg/ml LBP pre-treatment significantly alleviated 24-h ethanol exposure-induced overexpression of TXNIP, increased cellular apoptosis, secretion of inflammatory cytokines, activation of NLRP3 inflammasome, production of ROS, and reduced antioxidant enzyme expression. Silence of TXNIP suppressed the activated NLRP3 inflammasome, increased oxidative stress and worsened apoptosis in the cells. Further addition of LBP did not influence the effects of TXNIP inhibition on the cells. In conclusion, inhibition of hepatic TXNIP by LBP contributes to the reduction of cellular apoptosis, oxidative stress and NLRP3 inflammasome-mediated inflammation.
Fang Huang - One of the best experts on this subject based on the ideXlab platform.
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quercetin luteolin and epigallocatechin gallate alleviate txnip and nlrp3 mediated inflammation and apoptosis with regulation of ampk in endothelial cells
European Journal of Pharmacology, 2014Co-Authors: Jianjun Wu, Xiaoshan Xu, Yi Li, Fang HuangAbstract:Abstract Endoplasmic reticulum stress (ER stress)-associated thioredoxin-interacting protein (TXNIP) and NOD-like Receptor pyrin domain containing-3 (NLRP3) signaling is a key event in the endothelial dysfunction. It induces the IL-1β production and thus accounts for inflammation and cell death. Quercetin, luteolin and epigallocatechin gallate (EGCG) are flavonoids with beneficial effects on cardiovascular functions, and we wondered whether these flavonoids protect endothelial functions against ER stress-associated impairments. Palmitate stimulation evoked oxidative stress and then induced TXNIP and NLRP3 inflammasome activation in the endothelial cells. Quercetin, luteolin and EGCG reduced reactive oxygen species production and inhibited TXNIP and NLRP3 inflammasome activation, lead to the downregulation of IL-1β expression. Meanwhile, these agents protected cells from apoptosis by restoration of mitochondrial membrane potential (Δψm) and inhibition of caspase-3 activity. PA stimulation induced inflammation accompanied by the loss of NO production in endothelial cells, but these alterations were reversed by treatment with quercetin, luteolin and EGCG. Co-treatment with AMPK inhibitor compound C diminished the beneficial effects of these flavonoids, suggesting the involvement of AMPK. In conclusion, quercetin, luteolin and EGCG inhibited ER stress-associated TXNIP and NLRP3 inflammasome activation, and thereby protected endothelial cells from inflammatory and apoptotic damage.
Susanne Eschenburg - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of the leucine rich repeat domain of the nod like Receptor nlrp1 implications for binding of muramyl dipeptide
FEBS Letters, 2014Co-Authors: Thomas F Reubold, Gernot Hahne, Sabine Wohlgemuth, Susanne EschenburgAbstract:The NOD-like Receptor NLRP1 (NLR family, pyrin domain containing 1) senses the presence of the bacterial cell wall component l-muramyl dipeptide (MDP) inside the cell. We determined the crystal structure of the LRR domain of human NLRP1 in the absence of MDP to a resolution of 1.65 A. The fold of the structure can be assigned to the ribonuclease inhibitor-like class of LRR proteins. We compared our structure with X-ray models of the LRR domains of NLRX1 and NLRC4 and a homology model of the LRR domain of NOD2. We conclude that the MDP binding site of NLRP1 is not located in the LRR domain.
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Crystal structure of the leucine‐rich repeat domain of the NOD‐like Receptor NLRP1: Implications for binding of muramyl dipeptide
FEBS Letters, 2014Co-Authors: Thomas F Reubold, Gernot Hahne, Sabine Wohlgemuth, Susanne EschenburgAbstract:Abstract The NOD-like Receptor NLRP1 (NLR family, pyrin domain containing 1) senses the presence of the bacterial cell wall component l -muramyl dipeptide (MDP) inside the cell. We determined the crystal structure of the LRR domain of human NLRP1 in the absence of MDP to a resolution of 1.65 A. The fold of the structure can be assigned to the ribonuclease inhibitor-like class of LRR proteins. We compared our structure with X-ray models of the LRR domains of NLRX1 and NLRC4 and a homology model of the LRR domain of NOD2. We conclude that the MDP binding site of NLRP1 is not located in the LRR domain.
Richard A Flavell - One of the best experts on this subject based on the ideXlab platform.
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regulation of the antimicrobial response by nlr proteins
Immunity, 2011Co-Authors: Eran Elinav, Richard A Flavell, Till Strowig, Jorge HenaomejiaAbstract:Nucleotide-binding, oligomerization domain (NOD)-like Receptor (NLR) proteins are a family of innate immune Receptors that play a pivotal role in microbial sensing, leading to the initiation of antimicrobial immune responses. Dysregulation of the function of multiple NLR family members has been linked, both in mice and humans, to a propensity for infection and autoinflammatory disease. Despite our increased understanding of NLR function and interactions, many aspects related to mechanisms of sensing, downstream signaling, and in vivo functions remain elusive. In this review, we focus on key members of the NLR family, describing their activation by diverse microbes, downstream effector functions, and interactions with each other and with other innate sensor protein families. Also discussed is the role of microbial sensing by NLR Receptors leading to activation of the adaptive immune arm that collaborates in the antimicrobial defense.
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inflammation induced tumorigenesis in the colon is regulated by caspase 1 and nlrc4
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Bo Hu, Stephanie C. Eisenbarth, Till Strowig, Eran Elinav, Samuel Huber, Carmen J Booth, Richard A FlavellAbstract:Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association is currently unknown. The inflammasome, a multiprotein complex formed by NOD-like Receptor (NLR) family members, has recently been shown to orchestrate multiple innate and adaptive immune responses, yet its potential role in inflammation-induced cancer has been little studied. Using the azoxymethane and dextran sodium sulfate colitis-associated colorectal cancer model, we show that caspase-1–deficient (Casp1−/−) mice have enhanced tumor formation. Surprisingly, the role of caspase-1 in tumorigenesis was not through regulation of colonic inflammation, but rather through regulation of colonic epithelial cell proliferation and apoptosis. Consequently, caspase-1–deficient mice demonstrate increased colonic epithelial cell proliferation in early stages of injury-induced tumor formation and reduced apoptosis in advanced tumors. We suggest a model in which the NLRC4 inflammasome is central to colonic inflammation-induced tumor formation through regulation of epithelial cell response to injury.
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nlrc4 ipaf a card carrying member of the nlr family
Clinical Immunology, 2009Co-Authors: Fayyaz S Sutterwala, Richard A FlavellAbstract:The NOD-like Receptor (NLR) family of proteins is involved in the regulation of innate immune responses and cell death pathways. Recent findings show that the NLR family member NLRC4 (also known as IPAF) has important roles in innate immune responses to Gram-negative bacteria. Macrophages infected with Legionella pneumophila, Salmonella typhimurium, Shigella flexneri, or Pseudomonas aeruginosa activate caspase-1 in an NLRC4-dependent manner leading to macrophage cell death and the release of proinflammatory cytokines. This review will discuss these findings as well as the role of bacterial type III and type IV secretion systems and flagellin in NLRC4-mediated caspase-1 activation.
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NLRC4/IPAF: a CARD carrying member of the NLR family
Clinical Immunology, 2008Co-Authors: Fayyaz S Sutterwala, Richard A FlavellAbstract:The NOD-like Receptor (NLR) family of proteins is involved in the regulation of innate immune responses and cell death pathways. Recent findings show that the NLR family member NLRC4 (also known as IPAF) has important roles in innate immune responses to Gram-negative bacteria. Macrophages infected with Legionella pneumophila, Salmonella typhimurium, Shigella flexneri, or Pseudomonas aeruginosa activate caspase-1 in an NLRC4-dependent manner leading to macrophage cell death and the release of proinflammatory cytokines. This review will discuss these findings as well as the role of bacterial type III and type IV secretion systems and flagellin in NLRC4-mediated caspase-1 activation.
Pinlan Li - One of the best experts on this subject based on the ideXlab platform.
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nod like Receptor protein 3 nlrp3 inflammasome activation and podocyte injury via thioredoxin interacting protein txnip during hyperhomocysteinemia
Journal of Biological Chemistry, 2014Co-Authors: Justine M Abais, Guangbi Li, Sabena M Conley, Krishna M Boini, Todd W.b. Gehr, Yang Chen, Pinlan LiAbstract:Abstract NADPH oxidase-derived reactive oxygen species (ROS) have been reported to activate NLRP3 inflammasomes resulting in podocyte and glomerular injury during hyperhomocysteinemia (hHcys). However, the mechanism by which the inflammasome senses ROS is still unknown in podocytes upon hHcys stimulation. The current study explored whether thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of the antioxidant thioredoxin and ROS sensor, mediates hHcys-induced NLRP3 inflammasome activation and consequent glomerular injury. In cultured podocytes, size exclusion chromatography and confocal microscopy showed that inhibition of TXNIP by siRNA or verapamil prevented Hcys-induced TXNIP protein recruitment to form NLRP3 inflammasomes and abolished Hcys-induced increases in caspase-1 activity and IL-1β production. TXNIP inhibition protected podocytes from injury as shown by normal expression levels of podocyte markers, podocin and desmin. In vivo, adult C57BL/6J male mice were fed a folate-free diet for 4 weeks to induce hHcys, and TXNIP was inhibited by verapamil (1 mg/ml in drinking water) or by local microbubble-ultrasound TXNIP shRNA transfection. Evidenced by immunofluorescence and co-immunoprecipitation studies, glomerular inflammasome formation and TXNIP binding to NLRP3 were markedly increased in mice with hHcys but not in TXNIP shRNA-transfected mice or those receiving verapamil. Furthermore, TXNIP inhibition significantly reduced caspase-1 activity and IL-1β production in glomeruli of mice with hHcys. Correspondingly, TXNIP shRNA transfection and verapamil attenuated hHcys-induced proteinuria, albuminuria, glomerular damage, and podocyte injury. In conclusion, our results demonstrate that TXNIP binding to NLRP3 is a key signaling mechanism necessary for hHcys-induced NLRP3 inflammasome formation and activation and subsequent glomerular injury.