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Inflammasome and the kidneys

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https://www.readbyqxmd.com/read/29336982/il-6-receptor-blockade-ameliorates-diabetic-nephropathy-via-inhibiting-inflammasome-in-mice
#1
Rui Wu, Xuanchen Liu, Jianyong Yin, Huijuan Wu, Xiulei Cai, Niansong Wang, Youcun Qian, Feng Wang
BACKGROUND AND OBJECTIVE: Interleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus. METHODS: Twelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed...
January 11, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29317641/zika-virus-infection-induces-host-inflammatory-responses-by-facilitating-nlrp3-inflammasome-assembly-and-interleukin-1%C3%AE-secretion
#2
Wenbiao Wang, Geng Li, De Wu, Zhen Luo, Pan Pan, Mingfu Tian, Yingchong Wang, Feng Xiao, Aixin Li, Kailang Wu, Xiaohong Liu, Lang Rao, Fang Liu, Yingle Liu, Jianguo Wu
Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection. The NLRP3 inflammasome plays a key role in host innate immune responses by activating caspase-1 to facilitate interleukin-1β (IL-1β) secretion. Here we report that ZIKV stimulates IL-1β secretion in infected patients, human PBMCs and macrophages, mice, and mice BMDCs. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29305119/weicao-capsule-ameliorates-renal-injury-through-increasing-autophagy-and-nlrp3-degradation-in-uan-rats
#3
Jiacai Hu, Hao Wu, Daochun Wang, Zhijie Yang, Lihua Zhuang, Na Yang, Junjun Dong
Uric acid nephropathy (UAN) is one of the most common metabolic diseases and leads to kidney damage. This study aimed to evaluate the effect of Weicao capsule on renal injury of UAN rats and to examine whether the mechanism was associated with induction of autophagy and degradation of nucleotide binding oligomerization domain (Nod)-like receptor (NLR) protein 3 (NLRP3) inflammasome. Sixty Sprague-Dawley rats were randomly allocated into 6 groups: Control, Model, Allopurinol, and Weicao (0.55/1.1/2.2 g/kg) group...
January 2, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29290137/small-leucine-rich-proteoglycans-in-renal-inflammation-two-sides-of-the-coin
#4
Madalina V Nastase, Andrea Janicova, Heiko Roedig, Louise Tzung-Harn Hsieh, Malgorzata Wygrecka, Liliana Schaefer
It is now well-established that members of the small leucine-rich proteoglycan (SLRP) family act in their soluble form, released proteolytically from the extracellular matrix (ECM), as danger-associated molecular patterns (DAMPs). By interacting with Toll-like receptors (TLRs) and the inflammasome, the two SLRPs, biglycan and decorin, autonomously trigger sterile inflammation. Recent data indicate that these SLRPs, besides their conventional role as pro-inflammatory DAMPs, additionally trigger anti-inflammatory signaling pathways to tightly control inflammation...
October 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29247045/the-immunology-of-hypertension
#5
REVIEW
Allison E Norlander, Meena S Madhur, David G Harrison
Although systemic hypertension affects a large proportion of the population, its etiology remains poorly defined. Emerging evidence supports the concept that immune cells become activated and enter target organs, including the vasculature and the kidney, in this disease. Mediators released by these cells, including reactive oxygen species, metalloproteinases, cytokines, and antibodies promote dysfunction of the target organs and cause damage. In vessels, these factors enhance constriction, remodeling, and rarefaction...
December 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29241624/the-macrophage-phenotype-and-inflammasome-component-nlrp3-contributes-to-nephrocalcinosis-related-chronic-kidney-disease-independent-from-il-1-mediated-tissue-injury
#6
Hans-Joachim Anders, Beatriz Suarez-Alvarez, Melissa Grigorescu, Orestes Foresto-Neto, Stefanie Steiger, Jyaysi Desai, Julian A Marschner, Mohsen Honarpisheh, Chongxu Shi, Jutta Jordan, Lisa Müller, Nicolai Burzlaff, Tobias Bäuerle, Shrikant R Mulay
Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis...
December 11, 2017: Kidney International
https://www.readbyqxmd.com/read/29169180/mitochondria-targeted-antioxidant-mito-tempo-protects-against-aldosterone-induced-renal-injury-in-vivo
#7
Wei Ding, Tingyan Liu, Xiao Bi, Zhiling Zhang
BACKGROUND/AIMS: Growing evidence suggests mitochondrial dysfunction (MtD) and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD) progression. We previously reported that Aldosterone (Aldo)-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS)-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo) could prevent Aldo-induced kidney damage in vivo...
November 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29138474/phagocytosis-of-environmental-or-metabolic-crystalline-particles-induces-cytotoxicity-by-triggering-necroptosis-across-a-broad-range-of-particle-size-and-shape
#8
Mohsen Honarpisheh, Orestes Foresto-Neto, Jyaysi Desai, Stefanie Steiger, Lidia Anguiano Gómez, Bastian Popper, Peter Boor, Hans-Joachim Anders, Shrikant R Mulay
In crystallopathies, crystals or crystalline particles of environmental and metabolic origin deposit within tissues, induce inflammation, injury and cell death and eventually lead to organ-failure. The NLRP3-inflammasome is involved in mediating crystalline particles-induced inflammation, but pathways leading to cell death are still unknown. Here, we have used broad range of intrinsic and extrinsic crystal- or crystalline particle-sizes and shapes, e.g. calcium phosphate, silica, titanium dioxide, cholesterol, calcium oxalate, and monosodium urate...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100270/albuminuria-confers-renal-resistance-to-loop-diuretics-via-the-stimulation-of-nlrp3-inflammasome-prostaglandin-signaling-in-thick-ascending-limb
#9
Yibo Zhuang, Zhanjun Jia, Caiyu Hu, Guixia Ding, Xintong Zhang, Yue Zhang, Guangrui Yang, Rajeev Rohatgi, Songming Huang, John Ci-Jiang He, Aihua Zhang
Renal resistance to loop diuretics is a frequent complication in a number of kidney disease patients with elusive mechanism. Employing human renal biopsy specimens, albumin overload mouse model, and primary cultures of mouse renal tubular cells, albuminuria effect on NKCC2 expression and function and the underlying mechanisms were investigated. In the renal biopsy specimens of albuminuric patients, we found that NKCC2 was significantly downregulated with a negative correlation with albuminuria severity as examined by immunohistochemistry...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093371/-identification-of-biomarkers-for-tubular-injury-and-interstitial-fibrosis-in-chronic-kidney-disease
#10
Shunsaku Nakagawa
 In chronic kidney disease (CKD), progressive nephron loss causes tubulointerstitial fibrosis and progressive tubular injury. Recent identification of the major cell populations of myofibroblast precursors in the kidney has enabled us to dissect the fibrogenic process after tubular injury. Kidney pericytes are a possible precursor of myofibroblasts, and may be promising targets for treating fibrogenesis. Our recent studies have shown that pericytes activate Toll-like receptor (TLR) 2/4- and myeloid differentiation primary response 88 (MyD88)-dependent proinflammatory signaling in response to renal tubular injury...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29091707/transcriptional-study-of-hyperoxaluria-and-calcium-oxalate-nephrolithiasis-in-male-rats-inflammatory-changes-are-mainly-associated-with-crystal-deposition
#11
Sunil Joshi, Wei Wang, Saeed R Khan
Hyperoxaluria associated with renal deposition of calcium oxalate (CaOx) crystals causes renal injury and inflammation leading to number of diseases including chronic kidney disease (CKD). It is however, not been possible to separate the renal consequences of hyperoxaluria from that of CaOx crystal deposition. We decided to utilize ethylene glycol (EG) model where hyperoxaluria and CaOx crystal deposition can be separated in time. To test our hypothesis, male rats were made hyperoxaluric by administering EG, rats were euthanized and kidneys were extracted on day 14, when occasional crystal is seen in the kidneys and day 28, when all animals have developed renal CaOx crystal deposits...
2017: PloS One
https://www.readbyqxmd.com/read/29072703/bcl6-attenuates-renal-inflammation-via-negative-regulation-of-nlrp3-transcription
#12
Dan Chen, Xiao-Qing Xiong, Ying-Hao Zang, Ying Tong, Bing Zhou, Qi Chen, Yue-Hua Li, Xing-Ya Gao, Yu-Ming Kang, Guo-Qing Zhu
Renal inflammation contributes to the pathogeneses of hypertension. This study was designed to determine whether B-cell lymphoma 6 (BCL6) attenuates renal NLRP3 inflammasome activation and inflammation and its underlying mechanism. Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used in the present study. Angiotensin (Ang) II or lipopolysaccharides (LPS) was used to induce inflammation in HK-2 cells, a human renal tubular epithelial (RTE) cell line. NLRP3 inflammasome was activated and BCL6 was downregulated in the kidneys of SHR...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29045935/emodinol-ameliorates-urate-nephropathy-by-regulating-renal-organic-ion-transporters-and-inhibiting-immune-inflammatory-responses-in-rats
#13
Hui Wu, Mengze Zhou, Guo Lu, Zhonglin Yang, Hui Ji, Qinghua Hu
Emodinol, 1β, 3β, 23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our Research Group, was identified with apparent uricosuric and nephroprotective effects in hyperuricemia mice in our previous study. This study aimed to investigate the renal protective effect of emodinol in urate nephropathy rats. Rats were orally administrated by combined adenine and ethambutol to induce urate nephropathy. Emodinol at various doses were administered intragastrically to urate nephropathy rats daily...
October 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29031829/gain-of-function-variants-in-nlrp1-protect-against-the-development-of-diabetic-kidney-disease-nlrp1-inflammasome-role-in-metabolic-stress-sensing
#14
Jaine L S Soares, Fernanda Pereira Fernandes, Thiago Andrade Patente, Maria B Monteiro, Maria C Parisi, Daniel Giannella-Neto, Maria L Corrêa-Giannella, Alessandra Pontillo
Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (padj<0...
October 12, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28988993/characterization-and-functional-assessment-of-the-nlrc3-like-molecule-of-the-goldfish-carassius-auratus-l
#15
Jiasong Xie, Miodrag Belosevic
The NLRC3-like (NLRC3L) molecule from the goldfish transcriptome database was identified and characterized. Quantitative gene expression analysis revealed the highest mRNA levels of NLRC3L were in the spleen and intestine, with lower mRNA levels observed in muscle and liver. Goldfish NLRC3L was differentially expressed in goldfish immune cell populations with highest mRNA levels measured in PBLs and macrophages. We generated a recombinant form of the molecule (rgfNLRC3L) and an anti-CT-NLRC3L IgG. Treatment of goldfish primary kidney macrophages in vitro with ATP, LPS and heat-killed Aeromonas salmonicida up-regulated the NLRC3L mRNA and protein...
October 6, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28956480/distinct-expression-profile-and-histological-distribution-of-nlrp3-inflammasome-components-in-the-tissues-of-hainan-black-goat-suggest-a-site-specific-role-in-the-inflammatory-response
#16
Kaizhao Zhang, Pan Tao, Jianxin Liu, Qingnan Wang, Shikun Ge, Zhangyong Ning
The NOD-like receptor protein 3 (NLRP3) inflammasome comprised of NLRP3, ASC and caspase-1 plays an important role in the inflammatory and innate immune response. However, little is known about the expression pattern and histological distribution of these genes in goat. Here, we first cloned the fulllength cDNAs of the NLRP3, ASC and caspase-1 genes of Hainan black goat and produced their polyclonal antibodies. Tissue-specific expression and histological distribution of these genes were analysed. Phylogenetic analysis revealed that these three goat genes had high homology with Bos taurus genes and low homology with avian or fish genes...
September 2017: Acta Veterinaria Hungarica
https://www.readbyqxmd.com/read/28933050/toll-like-receptor-4-signaling-mediates-inflammation-and-tissue-injury-in-diabetic-nephropathy
#17
REVIEW
Giacomo Garibotto, Annalisa Carta, Daniela Picciotto, Francesca Viazzi, Daniela Verzola
Toll-like receptors (TLRs) are a class of receptors of the innate immune system which detect pathogen-associated and danger-associated molecular patterns in order to initiate an inflammatory response. TLR2 and TLR4 downward signaling causes the production of proinflammatory cytokines that can induce insulin resistance and cardiovascular damage in obesity and type 2 diabetes mellitus. In diabetic nephropathy, TLR4, nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and NLRP3 inflammasome are involved in the production and persistence of inflammation...
September 20, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28918467/anisodamine-inhibits-endoplasmic-reticulum-stress-associated-txnip-nlrp3-inflammasome-activation-in-rhabdomyolysis-induced-acute-kidney-injury
#18
Xiaopeng Yuan, Yitao Zheng, Chuanbao Chen, Changxi Wang
Anisodamine protects against free radical-induced cellular damage. This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6 J mice, TXNIP(-/-) and NLRP3 (-/-) (both were C57BL/6 J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, and interleukin (IL-1α, IL-1β, and IL-18) were detected...
September 16, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28884615/resveratrol-loaded-nanoparticles-conjugated-with-kidney-injury-molecule-1-as-a-drug-delivery-system-for-potential-use-in-chronic-kidney-disease
#19
Yuh-Feng Lin, Yu-Hsuan Lee, Yung-Ho Hsu, Yi-Jie Chen, Yuan-Feng Lin, Fong-Yu Cheng, Hui-Wen Chiu
AIM: We used resveratrol (Res)-loaded nanoparticles (Res NPs) as a novel method for improving the pharmacokinetic properties of Res and analyzed the effect of Res NPs in chronic kidney disease (CKD). MATERIALS & METHODS: We coupled anti-kidney injury molecule-1 antibodies to Res NPs and analyzed safety and efficacy. RESULTS: Res NPs had low toxicity and induced autophagy. Res NPs inhibited the NLRP3 inflammasome and IL-1β secretion. Higher NLRP3 expression levels were observed in peripheral blood monocytic cells of CKD patients than healthy individuals...
September 8, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28878231/dietary-iron-restriction-alleviates-renal-tubulointerstitial-injury-induced-by-protein-overload-in-mice
#20
Yasumasa Ikeda, Yuya Horinouchi, Hirofumi Hamano, Tasuku Hirayama, Seiji Kishi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Ken-Ichi Aihara, Hideko Nagasawa, Koichiro Tsuchiya, Toshiaki Tamaki
Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA)...
September 6, 2017: Scientific Reports
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