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Juan Zhan, Kun Wang, Conghui Zhang, Chunxiu Zhang, Yueqiang Li, Ying Zhang, Xiaoyan Chang, Qiaodan Zhou, Ying Yao, Yanyan Liu, Gang Xu
Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis...
2016: International Journal of Molecular Sciences
Farook Thameem, Sobha Puppala, Vidya S Farook, Balakuntalam S Kasinath, John Blangero, Ravindranath Duggirala, Hanna E Abboud
BACKGROUND/AIM: Toll-like receptor 4 (TLR4) is one of the regulators of the innate immune response. Genetic variations in TLR4 have been associated with inflammatory diseases, including type 2 diabetes. However, to our knowledge, there are no reports on the role of variations in TLR4 in chronic kidney disease susceptibility. The objective of this study is to determine whether the genetic variants in TLR4 are associated with the estimated glomerular filtration rate (eGFR), a measure of renal function...
August 2016: Cardiorenal Medicine
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
Koji Tsugawa, Tadaatsu Imaizumi, Shojiro Watanabe, Kazushi Tsuruga, Hidemi Yoshida, Hiroshi Tanaka
BACKGROUND: Signaling pathways induced by the activation of renal toll-like receptor 4 (TLR4) play a pivotal role in chronic kidney disease (CKD). Some recent studies suggested that clarithromycin (CAM), a 14-membered ring macrolide, exerts renoprotective effects by suppressing proinflammatory chemokines. However, its beneficial effects on signaling pathways through renal TLR4 activation are unknown. METHODS: Cultured human mesangial cells (MCs) were treated with lipopolysaccharide (LPS)...
September 10, 2016: Clinical and Experimental Nephrology
S B Anderberg, T Luther, R Frithiof
Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue...
September 7, 2016: Acta Physiologica
Cristian González-Guerrero, Pablo Cannata-Ortiz, Consuelo Guerri, Jesús Egido, Alberto Ortiz, Adrián M Ramos
Cyclosporine A (CsA) successfully prevents allograft rejection, but nephrotoxicity is still a dose-limiting adverse effect. TLR4 activation promotes kidney damage but whether this innate immunity receptor mediates CsA nephrotoxicity is unknown. The in vivo role of TLR4 during CsA nephrotoxicity was studied in mice co-treated with CsA and the TLR4 inhibitor TAK242 and also in TLR4(-/-) mice. CsA-induced renal TLR4 expression in wild-type mice. Pharmacological or genetic targeting of TLR4 reduced the activation of proinflammatory signaling, including JNK/c-jun, JAK2/STAT3, IRE1α and NF-κB and the expression of Fn14...
September 1, 2016: Archives of Toxicology
In Hee Kim, Jun Xu, Xiao Liu, Yukinori Koyama, Hsiao-Yen Ma, Karin Diggle, Young-Hyun You, Jan M Schilling, Dilip Jeste, Kumar Sharma, David A Brenner, Tatiana Kisseleva
We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction...
August 2016: Age (2005-)
Nur Arfian, Khusnul Muflikhah, Sri Kadarsih Soeyono, Dwi Cahyani Ratna Sari, Untung Tranggono, Nungki Anggorowati, Muhammad Mansyur Romi
Kidney fibrosis is the common final pathway of chronic kidney diseases (CKD). It is characterized by myofibroblast formation, inflammation, and epithelial architecture damage. Vitamin D is known as a renoprotective agent, although the precise mechanism is not well understood. This study aimed to elucidate the effect of vitamin D in fibroblast expansion, inflammation, and apoptosis in kidney fibrosis. We performed unilateral ureteral obstruction (UUO) in male Swiss-Webster background mice (3 months, 30-40 grams) to induce kidney fibrosis...
2016: Kobe Journal of Medical Sciences
Haiyan Fu, Zhansheng Hu, Xingwei Di, Qiuhong Zhang, Rongbin Zhou, Hongyang Du
Tenuigenin (TNG) has been reported to have various pharmacological activities, such as anti-oxidative and anti-inflammatory activities. However, the protective effects of TNG on lipopolysaccharides (LPS)-induced acute kidney injury (AKI) are still not clear. The aim of this study was to investigate the protective effects and mechanism of TGN on LPS-induced AKI in mice. The kidney histological change, levels of blood urea nitrogen (BUN), and creatinine were measured to assess the protective effects of TNG on LPS-induced AKI...
August 18, 2016: European Journal of Pharmacology
Qingsong Zhang, Gang Li, Li Xu, Qian Li, Qianyan Wang, Yue Zhang, Qing Zhang, Peng Sun
Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild‑type (C3H/HeN) and TLR4‑mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI)...
October 2016: Molecular Medicine Reports
Hye Sook Min, Jin Joo Cha, Kitae Kim, Jung Eun Kim, Jung Yeon Ghee, Hyunwook Kim, Ji Eun Lee, Jee Young Han, Lak Shin Jeong, Dae Ryong Cha, Young Sun Kang
The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888...
September 2016: Journal of Korean Medical Science
S C Zmonarski, K Kościelska-Kasprzak, M Banasik, M Myszka, M Żabińska, K Madziarska, O Mazanowska, M Krajewska, M Boratyńska, M Klinger
BACKGROUND: Both tacrolimus (Tac) and cyclosporine (CsA) inhibit control peripheral blood mononuclear cells (PBMC) after stimulation of various Toll-like receptors (TLR) at supra-pharmacological concentrations. Earlier studies demonstrated that 24 hours after kidney transplantation (KT), the expression of the TLR4 messenger RNA (mRNA) in PBMC from patients with subsequent delayed graft function (DGF+) was lower than in patients without DGF (DGF-). An assessment was made of the interaction of immunosuppression with TLR mRNA in PBMC and to verify whether the reduced expression of TLR-2,3,4,9 mRNA in PBMC is permanent in DGF+...
June 2016: Transplantation Proceedings
Anastasia Polycarpou, Martin J Holland, Ioannis Karageorgiou, Ayad Eddaoudi, Stephen L Walker, Sam Willcocks, Diana N J Lockwood
Toll-like receptor (TLR)-1 and TLR2 have been shown to be receptors for Mycobacterium leprae (M. leprae), yet it is unclear whether M. leprae can signal through alternative TLRs. Other mycobacterial species possess ligands for TLR4 and genetic association studies in human populations suggest that people with TLR4 polymorphisms may be protected against leprosy. Using human embryonic kidney (HEK)-293 cells co-transfected with TLR4, we demonstrate that M. leprae activates TLR4. We used human macrophages to show that M...
2016: Frontiers in Cellular and Infection Microbiology
Rachael E Tarlinton, Lauren Alder, Joanna Moreton, Grazieli Maboni, Richard D Emes, Sabine Tötemeyer
BACKGROUND: Toll like receptors are one of the major innate immune system pathogen recognition systems. There is little data on the expression of the TLR10 member of this family in the horse. RESULTS: This paper describes the genetic structure of the Equine TLR10 gene and its RNA expression in a range of horse tissues. It describes the phylogenetic analysis of the Equine TLR1,6,10,2 annotations in the horse genome, firmly identifying them in their corresponding gene clades compared to other species and firmly placing the horse gene with other TLR10 genes from odd-toed ungulates...
2016: BMC Research Notes
Meng Qi, Lianhong Yin, Lina Xu, Xufeng Tao, Yan Qi, Xu Han, Changyuan Wang, Youwei Xu, Huijun Sun, Kexin Liu, Jinyong Peng
We previously reported the potent effect of dioscin against renal ischemia/reperfusion injury, but little is known about the role of dioscin in lipopolysaccharide (LPS)-induced inflammatory kidney injury. The present work aimed to investigate the effects and potential mechanisms of dioscin in preventing LPS-induced kidney injury. In vivo injury was induced in rats and mice with an intraperitoneal injection of LPS (10mg/kg), and in vitro studies were performed on NRK-52E and HK-2 cells challenged with LPS (0...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Alessandra Stasi, Angelica Intini, Chiara Divella, Rossana Franzin, Eustacchio Montemurno, Giuseppe Grandaliano, Claudio Ronco, Enrico Fiaccadori, Giovanni Battista Pertosa, Loreto Gesualdo, Giuseppe Castellano
Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT)...
July 6, 2016: Nephrology, Dialysis, Transplantation
Xiaoqing Chen, Lanlan Cui, Rongda Li, Huili Lin, Ziyang Huang, Ling Lin
OBJECTIVES: This study was designed to establish a murine model of lupus with atherosclerosis, and to investigate the expression of Toll-like receptors (TLRs) in the aorta and kidney. METHODS: The 9-week-old female ApoE-/- and C57BL/6 mice were randomly divided into a ApoE-/- pristane treated group (group A), ApoE-/- control group (group B), C57BL/6 pristane treated group (group C) and C57BL/6 control group (group D). Each mouse was given either a single intraperitoneal injection of 0...
July 2016: Clinical and Experimental Rheumatology
Yi Shao, Minglei Sha, Lei Chen, Deng Li, Jun Lu, Shujie Xia
Percutaneous nephrolithotomy (PCNL) causes a rapid increase in renal pelvic pressure in the kidney, which induces an inflammatory response. High-mobility group box-1 (HMGB1) is known to trigger the recruitment of inflammatory cells and the release of pro-inflammatory cytokines following ischemia reperfusion injury in the kidney, but the contribution of HMGB1 to the inflammatory response following high-pressure renal pelvic perfusion has not been investigated. In this study, high-pressure renal pelvic perfusion was induced in anesthetized pigs to examine the effect of HMGB1 on the inflammatory response...
June 29, 2016: American Journal of Physiology. Renal Physiology
Bruns A Watts, Thampi George, Andrew Badalamenti, David W Good
High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3 (-) absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral receptor for advanced glycation end products (RAGE)-dependent pathway that is additive to Toll-like receptor 4 (TLR4)-ERK-mediated inhibition by LPS (Good DW, George T, Watts BA III...
September 1, 2016: American Journal of Physiology. Renal Physiology
Hiroyuki Inagawa, Toshiyuki Saika, Takashi Nisizawa, Chie Kohchi, Maya Uenobe, Gen-Ichiro Soma
BACKGROUND/AIM: Oral ingestion of lipopolysaccharide (LPS) has been shown to be effective in diseases' prevention. Brown rice contains large amounts of LPS not actively consumed because of bad taste. Recently, a new type of brown rice with its wax layer removed has been produced. In this report, we measured the LPS content of this dewaxed rice and evaluated the function of innate immune activation on macrophages. MATERIALS AND METHODS: Dewaxed brown rice and polished rice were prepared using the Saika-style rice polishing process...
July 2016: Anticancer Research
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