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Inflammasome and the kidneys

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https://www.readbyqxmd.com/read/28437591/fluorofenidone-attenuates-il-1%C3%AE-production-by-interacting-with-nlrp3-inflammasome-in-unilateral-ureteral-obstruction
#1
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
#2
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...
April 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28404641/nlrp3-inflammasome-as-a-novel-target-for-docosahexaenoic-acid-metabolites-to-abrogate-glomerular-injury
#3
Guangbi Li, Zhida Chen, Owais M Bhat, Qinghua Zhang, Justine M Abais-Battad, Sabena M Conley, Joseph K Ritter, Pin-Lan Li
The NOD-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 NLRP3 inflammasome can be a therapeutic target for treatment of hHcys-induced kidney injury. Given that docosahexaenoic acid (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...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28391347/therapeutics-for-apol1-nephropathies-putting-out-the-fire-in-the-podocyte
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28097088/icariin-ameliorates-iga-nephropathy-by-inhibition-of-nuclear-factor-kappa-b-nlrp3-pathway
#16
Lei Zhang, Xing-Zhi Wang, Yu-Shu Li, Lei Zhang, Li-Rong Hao
Immunoglobulin A nephropathy (IgAN) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti-inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in IgAN rats and the mechanisms behind these effects. IgAN model was established in Sprague-Dawley rats by oral and intravenous immunization with bovine gamma-globulin for 12 weeks, and rats were treated with icariin from 12 to 18 weeks...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28038382/the-nlrp3-inflammasome-is-a-potential-target-of-ozone-therapy-aiming-to-ease-chronic-renal-inflammation-in-chronic-kidney-disease
#17
Gang Yu, Zhiming Bai, Zhiyuan Chen, Hui Chen, Guoren Wang, Gang Wang, Zhenxiang Liu
Ozone therapy is an effective medical treatment for various diseases. A previous study has demonstrated its reno-protective effect in chronic kidney disease (CKD), but the mechanism involved is not completely known. This study produced the 5/6 nephrectomized CKD rat model and investigated whether the reno-protective effect of ozone therapy was achieved by its anti-inflammatory property through the modulation of the NLRP3 inflammasome. The results showed that ozone therapy at a low concentration improved renal function and ameliorated renal morphological injury in 5/6 nephrectomized rats...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28000751/suppression-of-nlrp3-inflammasome-activation-ameliorates-chronic-kidney-disease-induced-cardiac-fibrosis-and-diastolic-dysfunction
#18
Antoinette Bugyei-Twum, Armin Abadeh, Kerri Thai, Yanling Zhang, Melissa Mitchell, Golam Kabir, Kim A Connelly
Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932476/high-fat-diet-induced-lysosomal-dysfunction-and-impaired-autophagic-flux-contribute-to-lipotoxicity-in-the-kidney
#19
Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomonori Kimura, Tomoko Namba, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Excessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27927859/systemic-elevation-of-proinflammatory-interleukin-18-in-hiv-hcv-coinfection-versus-hiv-or-hcv-monoinfection
#20
Rebecca T Veenhuis, Jacquie Astemborski, Michael A Chattergoon, Paige Greenwood, Marissa Jarosinski, Richard D Moore, Shruti H Mehta, Andrea L Cox
BACKGROUND: HIV/HCV coinfection and elevated interleukin (IL)-18 levels are both associated with enhanced progression of hepatic inflammation and increased risk of diabetes, kidney disease, and cardiovascular disease. IL-18 is a proinflammatory cytokine made upon activation of the inflammasome, an innate sensing system. We assessed whether increased IL-18 could explain the increased incidence and progression of inflammatory conditions seen with HIV/HCV coinfection. METHODS: Serum from 559 subjects with HIV monoinfection, HCV monoinfection, HIV/HCV coinfection, or people who inject drugs with neither infection was tested for IL-18 by ELISA and for 16 other analytes by electrochemiluminescence immunoassay...
December 7, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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