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Inflammasome and the kidneys

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https://www.readbyqxmd.com/read/28631886/nlrp3-expression-and-urinary-hsp72-in-relation-to-biomarkers-of-inflammation-and-oxidative-stress-in-diabetic-nephropathy-patients
#1
Hemat El-Sayed El-Horany, Rania Nagi Abd-Ellatif, Mona Watany, Yasser M Hafez, Hanaa Ibrahim Okda
Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN...
June 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28628921/activation-of-cox-2-mpges-1-pge2-cascade-via-nlrp3-inflammasome-contributes-to-albumin-induced-proximal-tubule-cell-injury
#2
Yibo Zhuang, Fei Zhao, Jing Liang, Xu Deng, Yue Zhang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Songming Huang
BACKGROUND/AIMS: The activation of NOD-like receptor family, pyrin domain containing3 (NLRP3) inflammasome has been shown to be positively correlated with the severity of proteinuria in chronic kidney disease (CKD) patients. Prostaglandin E2 (PGE2), an important inflammatory mediator, is also involved in various kidney injuries. The aim of the present study was to investigate the involvement of NLRP3 inflammasome and PGE2 synthetic pathway in albumin-induced renal tubular injury. METHODS: Murine proximal tubular cells (mPTCs) were treated with albumin to induce cell injury...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28614830/expression-of-tlr2-nod1-and-nod2-and-the-nlrp3-inflammasome-in-renal-tubular-epithelial-cells-of-male-versus-female-mice
#3
Sean E DeWolf, Alana A Shigeoka, Andrew Scheinok, Sashi G Kasimsetty, Alexander K Welch, Dianne B McKay
BACKGROUND: Gender-biased outcomes are associated with acute kidney injury (AKI) and human and animal studies have shown that females are preferentially protected from renal ischemia. However, the reason for this is not known. One clue might lie with pattern recognition receptors (PRRs), which are triggers of ischemic injury when ligated by molecules in the ischemic milieu. Several PRR families are expressed by renal tubular epithelial cells (RTEs) and incite cell death signaling and production of pro-inflammatory molecules...
June 15, 2017: Nephron
https://www.readbyqxmd.com/read/28588189/metabolic-injury-induced-nlrp3-inflammasome-activation-dampens-phospholipid-degradation
#4
Elena Rampanelli, Evelyn Orsó, Peter Ochodnicky, Gerhard Liebisch, Pieter J Bakker, Nike Claessen, Loes M Butter, Marius A van den Bergh Weerman, Sandrine Florquin, Gerd Schmitz, Jaklien C Leemans
The collateral effects of obesity/metabolic syndrome include inflammation and renal function decline. As renal disease in obesity can occur independently of hypertension and diabetes, other yet undefined causal pathological pathways must be present. Our study elucidate novel pathological pathways of metabolic renal injury through LDL-induced lipotoxicity and metainflammation. Our in vitro and in vivo analysis revealed a direct lipotoxic effect of metabolic overloading on tubular renal cells through a multifaceted mechanism that includes intralysosomal lipid amassing, lysosomal dysfunction, oxidative stress, and tubular dysfunction...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28459555/ameliorative-effect-of-ecklonia-cava-polyphenol-extract-on-renal-inflammation-associated-with-aberrant-energy-metabolism-and-oxidative-stress-in-high-fat-diet-induced-obese-mice
#5
Hyeyoon Eo, Ji Eun Park, You-Jin Jeon, Yunsook Lim
Immoderate fat accumulation causes both oxidative stress and inflammation, which can induce kidney damage in obesity. Previously, Ecklonia cava has shown anti-inflammatory and antioxidative effects. Our group aimed to investigate whether E. cava polyphenol extract (ECPE) improves renal damage in high fat diet (HFD)-induced obese mice through regulation of not only energy metabolism but also oxidative stress and inflammation. After obesity induction by HFD, the mice were treated with different dosages of ECPE (100 or 500 mg/kg/day) by gavage for 12 weeks...
May 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28437591/fluorofenidone-attenuates-il-1%C3%AE-production-by-interacting-with-nlrp3-inflammasome-in-unilateral-ureteral-obstruction
#6
Linfeng Zheng, Jin Zhang, Xiangning Yuan, Juan Tang, Sisi Qiu, Zhangzhe Peng, Qiongjing Yuan, Yanyun Xie, Wenjuan Mei, Yiting Tang, Jie Meng, Gaoyun Hu, Lijian Tao
AIM: We explored whether Fluorofenidone reduced IL-1β production by interacting with NLRP3 inflammasome in unilateral ureteral obstruction (UUO). METHODS: UUO rats were treated with Fluorofenidone (500 mg · kg · d) for 3, 7 days. Morphologic analysis and leukocytes infiltration were assessed in ligated kidneys. Furthermore, plasmids of NLRP3, ASC, pro-Caspase-1, pro-IL-1β were co-transfected into 293 T cells, and then treated with Fluorofenidone (2 mM)...
April 24, 2017: Nephrology
https://www.readbyqxmd.com/read/28428988/polydatin-attenuates-potassium-oxonate-induced-hyperuricemia-and-kidney-inflammation-by-inhibiting-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-via-the-ampk-sirt1-pathway
#7
Lvyi Chen, Zhou Lan
This study was designed to investigate the effects of polydatin (PLD) on potassium oxonate-induced hyperuricemic rats. Hyperuricemic rats were treated with potassium oxonate (250 mg kg(-1)) intragastrically for 7 days, and polydatin (25, 50 mg kg(-1)) or allopurinol (5 mg kg(-1)) was administered to the rats 1 h after the potassium oxonate exposure. Polydatin administration decreased the levels of uric acid and creatinine in serum and urine, leading to inhibition of pro-inflammatory cytokine production in serum and kidney...
May 24, 2017: Food & Function
https://www.readbyqxmd.com/read/28404641/nlrp3-inflammasome-as-a-novel-target-for-docosahexaenoic-acid-metabolites-to-abrogate-glomerular-injury
#8
Guangbi Li, Zhida Chen, Owais M Bhat, Qinghua Zhang, Justine M Abais-Battad, Sabena M Conley, Joseph K Ritter, Pin-Lan Li
The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and glomerular sclerosis during hyperhomocysteinemia (hHcys). However, it remains unclear whether the NLRP3 inflammasome can be a therapeutic target for treatment of hHcys-induced kidney injury. Given that DHA metabolites-resolvins have potent anti-inflammatory effects, the present study tested whether the prototype, resolvin D1 (RvD1), and 17S-hydroxy DHA (17S-HDHA), an intermediate product, abrogate hHcys-induced podocyte injury by targeting the NLRP3 inflammasome...
June 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28391347/therapeutics-for-apol1-nephropathies-putting-out-the-fire-in-the-podocyte
#9
Jurgen Heymann, Cheryl A Winkler, Maarten Hoek, Katalin Susztak, Jeffrey B Kopp
APOL1 nephropathies comprise a range of clinical and pathologic syndromes, which can be summarized as focal segmental glomerulosclerosis, in various guises, and arterionephrosclerosis, otherwise known as hypertensive kidney diseases. Current therapies for these conditions may achieve therapeutic targets, reduction in proteinuria and control of blood pressure, respectively, but often fail to halt the progressive decline in kidney function. It appears that current therapies fail to address certain underlying critical pathologic processes that are driven, particularly in podocytes and microvascular cells, by the APOL1 renal risk genetic variants...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28374152/uric-acid-activates-nrlp3-inflammasome-in-an-in-vivo-model-of-epithelial-to-mesenchymal-transition-in-the-kidney
#10
César Andrés Romero, Aline Remor, Alexandra Latini, Ana Lucía De Paul, Alicia Inés Torres, Jorge Humberto Mukdsi
Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics...
April 3, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28348462/nlrp3-deficiency-attenuates-renal-fibrosis-and-ameliorates-mitochondrial-dysfunction-in-a-mouse-unilateral-ureteral-obstruction-model-of-chronic-kidney-disease
#11
Honglei Guo, Xiao Bi, Ping Zhou, Shijian Zhu, Wei Ding
Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28218266/crystal-nephropathies-mechanisms-of-crystal-induced-kidney-injury
#12
REVIEW
Shrikant R Mulay, Hans-Joachim Anders
Crystals can trigger a wide range of kidney injuries that can lead to acute kidney injury, chronic kidney disease, renal colic or nephrocalcinosis, depending on the localization and dynamics of crystal deposition. Studies of the biology of crystal handling by the kidney have shown that the formation of different crystals and other microparticles and the associated mechanisms of renal damage share molecular mechanisms, such as stimulation of the NLRP3 inflammasome or direct cytotoxicity through activation of the necroptosis signalling pathway...
April 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28215032/nlrp3-inflammasome-activation-regulated-by-nf-%C3%AE%C2%BAb-and-dapk-contributed-to-paraquat-induced-acute-kidney-injury
#13
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
https://www.readbyqxmd.com/read/28205387/fructose-down-regulates-mir-330-to-induce-renal-inflammatory-response-and-insulin-signaling-impairment-attenuation-by-morin
#14
Ting-Ting Gu, Lin Song, Tian-Yu Chen, Xin Wang, Xiao-Juan Zhao, Xiao-Qin Ding, Yan-Zi Yang, Ying Pan, Dong-Mei Zhang, Ling-Dong Kong
SCOPE: Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs (miRNAs) are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of morin against fructose-induced kidney injury, with particular focus on miR-330 expression change, inflammatory response and insulin signaling impairment. METHODS AND RESULTS: miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR)1/3 signaling, NF-κB/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively...
February 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28197935/anti-inflammatory-effect-of-total-saponin-fraction-from-dioscorea-nipponica-makino-on-gouty-arthritis-and-its-influence-on-nalp3-inflammasome
#15
Qi Zhou, Dong-Hua Yu, Ning Zhang, Shu-Min Liu
OBJECTIVE: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis (GA) in rats. METHODS: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin (900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the mRNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats' peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively...
February 15, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28193546/contribution-of-guanine-nucleotide-exchange-factor-vav2-to-nlrp3-inflammasome-activation-in-mouse-podocytes-during-hyperhomocysteinemia
#16
Sabena M Conley, Justine M Abais-Battad, Xinxu Yuan, Qinghua Zhang, Krishna M Boini, Pin-Lan Li
NADPH oxidase (NOX)-derived reactive oxygen species (ROS) have been demonstrated to mediate the activation of NOD-like receptor protein 3 (NLRP3) inflammasomes in podocytes in response to elevated levels of homocysteine (Hcys). However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The present study tested whether the guanine nucleotide exchange factor Vav2 mediates Rac1-mediated NOX activation in response to elevated Hcys leading to NLRP3 inflammasome activation in podocytes and consequent glomerular injury...
May 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28179433/il-36-signaling-facilitates-activation-of-the-nlrp3-inflammasome-and-il-23-il-17-axis-in-renal-inflammation-and-fibrosis
#17
Hsi-Hua Chi, Kuo-Feng Hua, Yu-Chuan Lin, Ching-Liang Chu, Chih-Yu Hsieh, Yu-Juei Hsu, Shuk-Man Ka, Yu-Ling Tsai, Feng-Cheng Liu, Ann Chen
IL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1...
February 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28151474/lincrna-gm4419-knockdown-ameliorates-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-mediated-inflammation-in-diabetic-nephropathy
#18
Hong Yi, Rui Peng, Lu-Yu Zhang, Yan Sun, Hui-Min Peng, Han-Deng Liu, Li-Juan Yu, Ai-Ling Li, Ya-Juan Zhang, Wen-Hao Jiang, Zheng Zhang
Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28143791/kidney-and-innate-immunity
#19
REVIEW
Ying-Hui Wang, Yu-Gen Zhang
Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28117341/nlrp3-inflammasome-pathogenic-role-and-potential-therapeutic-target-for-iga-nephropathy
#20
Yu-Ling Tsai, Kuo-Feng Hua, Ann Chen, Chyou-Wei Wei, Wen-Shiang Chen, Cheng-Yeu Wu, Ching-Liang Chu, Yung-Luen Yu, Chia-Wen Lo, Shuk-Man Ka
We have previously showed that IL-1β is involved in the pathogenesis of both spontaneously occurring and passively induced IgA nephropathy (IgAN) models. However, the exact causal-relationship between NLRP3 inflammasome and the pathogenesis of IgAN remains unknown. In the present study, we showed that [1] IgA immune complexes (ICs) activated NLRP3 inflammasome in macrophages involving disruption of mitochondrial integrity and induction of mitochondrial ROS, bone marrow-derived dendritic cells (BMDCs) and renal intrinsic cells; [2] knockout of NLRP3 inhibited IgA ICs-mediated activation of BMDCs and T cells; and [3] knockout of NLRP3 or a kidney-targeting delivery of shRNA of NLRP3 improved renal function and renal injury in a mouse IgAN model...
January 24, 2017: Scientific Reports
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