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Inflammasome and the kidneys

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https://www.readbyqxmd.com/read/27872860/danggui-buxue-tang-attenuates-tubulointerstitial-fibrosis-via-suppressing-nlrp3-inflammasome-in-a-rat-model-of-unilateral-ureteral-obstruction
#1
Linna Wang, Jiwei Ma, Cunxia Guo, Changyong Chen, Zhong Yin, Xueguang Zhang, Xiangmei Chen
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). This study aimed to characterize Danggui Buxue Tang (DBT) renoprotection and relationship with NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome expression in rats with unilateral ureteral obstruction (UUO). Sprague-Dawley rats were subjected to UUO and randomly assigned to untreated UUO, enalapril-treated (10 mg/kg/day), and DBT-treated (9 g/kg/day) groups. Sham-operated rats served as controls, with 8 rats in each group...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27869651/pericyte-myd88-and-irak4-control-inflammatory-and-fibrotic-responses-to-tissue-injury
#2
Irina A Leaf, Shunsaku Nakagawa, Bryce G Johnson, Jin Joo Cha, Kristen Mittelsteadt, Kevin M Guckian, Ivan G Gomez, William A Altemeier, Jeremy S Duffield
Fibrotic disease is associated with matrix deposition that results in the loss of organ function. Pericytes, the precursors of myofibroblasts, are a source of pathological matrix collagens and may be promising targets for treating fibrogenesis. Here, we have shown that pericytes activate a TLR2/4- and MyD88-dependent proinflammatory program in response to tissue injury. Similarly to classic immune cells, pericytes activate the NLRP3 inflammasome, leading to IL-1β and IL-18 secretion. Released IL-1β signals through pericyte MyD88 to amplify this response...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27867451/thioredoxin-interacting-protein-mediates-nlrp3-inflammasome-activation-involved-in-the-susceptibility-to-ischemic-acute-kidney-injury-in-diabetes
#3
Ye Da Xiao, Ya Yi Huang, Hua Xin Wang, Yang Wu, Yan Leng, Min Liu, Qian Sun, Zhong-Yuan Xia
Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI). However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP) expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R-) induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES) treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction)...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27863839/antihyperuricemic-effect-of-liquiritigenin-in-potassium-oxonate-induced-hyperuricemic-rats
#4
Long Hongyan, Wu Suling, Zhu Weina, Zhang Yajie, Ruan Jie
The aim is to investigate the anti-hyperuricemic and renal protective effects of liquiritigenin in potassium oxonate-induced hyperuricemic rats. Hyperuricemia in rats was induced were induced with potassium oxonate (250mg/kg) intragastrically for 7 days, and liquiritigenin (20, 40mg/kg) and allopurinol (5mg/kg) were daily administrated to the rats orally 1h after the potassium oxonate exposure. Liquiritigenin significantly reversed the elevated productions of uric acid in serum and urine and pro-inflammation cytokines in serum and kidney, which shown that liquiritigenin has renal protective effects...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27826011/roles-of-the-nlrp3-inflammasome-in-the-pathogenesis-of-diabetic-nephropathy
#5
REVIEW
Yuan-Ye Qiu, Li-Qin Tang
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and persistent inflammation in circulatory and renal tissues is an important pathophysiological basis for DN. The essence of the microinflammatory state is the innate immune response, which is central to the occurrence and development of DN. Members of the inflammasome family, including both "receptors" and "regulators", are key to the inflammatory immune response. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and other inflammasome components are able to detect endogenous danger signals, resulting in activation of caspase-1 as well as interleukin (IL)-1β, IL-18 and other cytokines; these events stimulate the inflammatory cascade reaction, which is crucial for DN...
November 5, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27819323/donor-and-recipient-genetic-variants-in-nlrp3-associate-with-early-acute-rejection-following-kidney-transplantation
#6
Mark C Dessing, Jesper Kers, Jeffrey Damman, Gerjan J Navis, Sandrine Florquin, Jaklien C Leemans
NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury. However, the role of NLRP3 in human renal disease is completely unknown. From a retrospective cohort study, we determined in 1271 matching donor and recipient samples if several NLRP3 single nucelotide polymorphisms (SNPs) were associated with primary non-function (PNF), delayed graft function (DGF), biopsy-proven acute rejection (BPAR) and death-censored graft and patient survival...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816762/long-term-administration-of-advanced-glycation-end-product-stimulates-the-activation-of-nlrp3-inflammasome-and-sparking-the-development-of-renal-injury
#7
Wan-Ju Yeh, Hsin-Yi Yang, Man-Hui Pai, Chi-Hao Wu, Jiun-Rong Chen
The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27784694/deficiency-of-mpges-1-exacerbates-renal-fibrosis-and-inflammation-in-mice-with-unilateral-ureteral-obstruction
#8
Renfei Luo, Yutaka Kakizoe, Feifei Wang, Xiang Fan, Shan Hu, Tianxin Yang, Weidong Wang, Chunling Li
Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 to prostaglandin E2 (PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. UUO was associated with increased renal PGE2 content and upregulated PGE2 receptor (EP) 4 expression in obstructed kidneys of both WT and KO mice; EP4 expression levels were higher in KO mice with UUO than that in WT mice...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27780585/purinergic-signaling-in-kidney-disease
#9
REVIEW
Robert I Menzies, Frederick W Tam, Robert J Unwin, Matthew A Bailey
Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function...
October 22, 2016: Kidney International
https://www.readbyqxmd.com/read/27769920/allopurinol-attenuates-rhabdomyolysis-associated-acute-kidney-injury-renal-and-muscular-protection
#10
Pedro H F Gois, Daniele Canale, Rildo A Volpini, Daniela Ferreira, Mariana M Veras, Vinicius Andrade-Oliveira, Niels O S Câmara, Maria H M Shimizu, Antonio C Seguro
BACKGROUND: Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. METHODS: Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol...
October 18, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27721494/nlrp3-inflammasome-mediates-contrast-media-induced-acute-kidney-injury-by-regulating-cell-apoptosis
#11
Jianxiao Shen, Ling Wang, Na Jiang, Shan Mou, Minfang Zhang, Leyi Gu, Xinghua Shao, Qin Wang, Chaojun Qi, Shu Li, Wanpeng Wang, Xiajing Che, Zhaohui Ni
Iodinated contrast media serves as a direct causative factor of acute kidney injury (AKI) and is involved in the progression of cellular dysfunction and apoptosis. Emerging evidence indicates that NLRP3 inflammasome triggers inflammation, apoptosis and tissue injury during AKI. Nevertheless, the underlying renoprotection mechanism of NLRP3 inflammasome against contrast-induced AKI (CI-AKI) was still uncertain. This study investigated the role of NLRP3 inflammasome in CI-AKI both in vitro and in vivo. In HK-2 cells and unilateral nephrectomy model, NLRP3 and NLRP3 inflammasome member ASC were significantly augmented with the treatment of contrast media...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721446/stabilization-of-endogenous-nrf2-by-minocycline-protects-against-nlrp3-inflammasome-induced-diabetic-nephropathy
#12
Khurrum Shahzad, Fabian Bock, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Sumra Nazir, Hongjie Wang, Shrey Kohli, Satish Ranjan, Peter R Mertens, Peter P Nawroth, Berend Isermann
While a plethora of studies support a therapeutic benefit of Nrf2 activation and ROS inhibition in diabetic nephropathy (dNP), the Nrf2 activator bardoxolone failed in clinical studies in type 2 diabetic patients due to cardiovascular side effects. Hence, alternative approaches to target Nrf2 are required. Intriguingly, the tetracycline antibiotic minocycline, which has been in clinical use for decades, has been shown to convey anti-inflammatory effects in diabetic patients and nephroprotection in rodent models of dNP...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27706238/involvement-of-the-nlrc4-inflammasome-in-diabetic-nephropathy
#13
Fang Yuan, Ryan Kolb, Gaurav Pandey, Wei Li, Lin Sun, Fuyou Liu, Fayyaz S Sutterwala, Yinghong Liu, Weizhou Zhang
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. The role of inflammation in DN has only recently been recognized. It has been shown that the NLRP3-inflammasome contributes to DN development by inducing interleukin (IL)-1β processing and secretion. In an effort to understand other IL-1β activating mechanism during DN development, we examined the role of the NLRC4-inflammasome in DN and found that NLRC4 is a parallel mechanism, in addition to the NLRP3-inflammasome, to induce pro-IL-1β processing and activation...
2016: PloS One
https://www.readbyqxmd.com/read/27640334/identification-and-expressional-analysis-of-nlrc5-inflammasome-gene-in-smolting-atlantic-salmon-salmo-salar
#14
Juan Pablo Pontigo, María José Agüero, Patricio Sánchez, Ricardo Oyarzún, Carolina Vargas-Lagos, Jorge Mancilla, Hans Kossmann, Francisco J Morera, Alejandro J Yáñez, Luis Vargas-Chacoff
The NOD-like receptors (NLRs) were recently identified as an intracellular pathogen recognition receptor family in vertebrates. While the immune system participation of NLRs has been characterized and analyzed in various mammalian models, few studies have considered NLRs in teleost species. Therefore, this study analyzed the Atlantic salmon (Salmo salar) NLRC5. Structurally, Atlantic salmon NLRC5 presented leucine-rich repeat subfamily genes. Phylogenetically, NLRC5 was moderately conserved between S. salar and other species...
September 15, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27620507/protective-effects-of-sirtuin-3-in-a-murine-model-of-sepsis-induced-acute-kidney-injury
#15
Wen-Yu Zhao, Lei Zhang, Ming-Xing Sui, You-Hua Zhu, Li Zeng
Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD(+) dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model...
September 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27616759/il-1%C3%AE-promotes-tubulointerstitial-injury-in-%C3%A2-mpo-anca-associated-glomerulonephritis%C3%A2
#16
Manabu Tashiro, Yoshie Sasatomi, Renya Watanabe, Maho Watanabe, Katsuhisa Miyake, Yasuhiro Abe, Tetsuhiko Yasuno, Kenji Ito, Naoko Ueki, Aki Hamauchi, Ritsuya Noda, Satoshi Hisano, Hitoshi Nakashima
BACKGROUND: It is widely accepted that tubulointerstitial injury (TII) is caused by glomerular injury (GI) in glomerular diseases. Glomerular endocapillary inflammation may result in crescent formation and exuded protein leakage, which may induce TII in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCAGN). However, some reports have indicated a glomerulonephritis-independent mechanism of TII in ANCAGN. The aim of this study was to determine the principle cytokines correlated with TII severity and to elucidate a characteristic mechanism for TII in ANCAGN...
October 2016: Clinical Nephrology
https://www.readbyqxmd.com/read/27600432/mitochondria-and-the-nlrp3-inflammasome-physiological-and-pathological-relevance
#17
REVIEW
Je-Wook Yu, Myung-Shik Lee
The NLRP3 inflammasome is assembled and activated in certain types of myeloid cells upon sensing microbe-derived toxins or host-derived danger signals. Activation of the NLRP3 inflammasome by endogenous ligands has been discovered in various disorders, including metabolic syndrome, type 2 diabetes, atherosclerosis, gout, reperfusion injury of the heart, neurodegeneration, such as Alzheimer's disease, chronic kidney diseases, and macular degeneration of the eyes. Despite the potential significance of the NLRP3 inflammasome in the pathogenesis of several diseases, details on the activation mechanism of the NLRP3 inflammasome by a variety of stimulators have yet to be reported...
November 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27547413/dipeptidyl-peptidase-4-inhibition-by-saxagliptin-prevents-inflammation-and-renal-injury-by-targeting-the-nlrp3-asc-inflammasome
#18
Yochai Birnbaum, Mandeep Bajaj, Jinqiao Qian, Yumei Ye
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor activation delays the progression of diabetic nephropathy (DN) in rodents. The NOD-like receptor 3 (Nlrp3) inflammasome plays an important role in DN. Dipeptidyl peptidase-4 inhibitors (DPP4I) inhibit the degradation of endogenous GLP-1 and various other active substances. We assessed whether DPP4I attenuates diabetes-induced activation of the inflammasome and progression of DN in mice with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM)...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27538510/inflammasome-activation-in-chronic-glomerular-diseases
#19
Sabena M Conley, Justine M Abais, Krishna M Boini, Pin-Lan Li
The intracellular multiprotein complex termed the inflammasome functions as a platform of pro-inflammatory cytokine production such as IL-1β and IL-18. Under certain conditions, however, the inflammasome produces non-canonical effects such as induction of cell death, pyroptosis and cell metabolism alterations. In mammalian cells, several types of inflammasomes were identified, but the most widely studied one is the inflammasome containing NOD-like receptor with pyrin domain 3 (NLRP3), which has recently been reported as a central pathogenic mechanism of chronic degenerative diseases...
August 17, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27536689/the-nucleotide-oligomerization-domain-like-receptors-in-kidney-injury
#20
REVIEW
Xiaojie Wang, Fan Yi
BACKGROUND: Inflammation is a hallmark of almost all forms of renal injury and the activation of the innate immune system is of importance in the development of many kidney diseases. Pattern recognition receptors (PRRs) act as sensors of the innate immune system to detect pathogen- or damage-associated molecular patterns, which initiate immune responses to resolve infections and repair damaged tissues. Abnormalities in PRR activation will lead to excessive inflammation. SUMMARY: Nucleotide oligomerization domain (NOD)-like receptors (NLRs) are recently identified intracellular PRRs that are essential to innate immune responses and tissue homeostasis...
April 2016: Kidney Diseases
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