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Nicolas S Merle, Anne Grunenwald, Marie-Lucile Figueres, Sophie Chauvet, Marie Daugan, Samantha Knockaert, Tania Robe-Rybkine, Remi Noe, Olivia May, Marie Frimat, Nathan Brinkman, Thomas Gentinetta, Sylvia Miescher, Pascal Houillier, Veronique Legros, Florence Gonnet, Olivier P Blanc-Brude, Marion Rabant, Regis Daniel, Jordan D Dimitrov, Lubka T Roumenina
Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology and clinical features. A frequent adverse effect related to massive hemolysis is the renal injury and inflammation. Nevertheless, it is still unclear whether heme--a danger-associated molecular pattern--and ligand for TLR4 or upstream hemolysis-derived products are responsible for these effects...
2018: Frontiers in Immunology
Kang Wang, Lei Hu, Jian-Kang Chen
Recent preclinical and clinical evidence suggests that hyperuricemia (HU) is an independent risk factor for metabolic syndrome, hypertension, cardiovascular disease and chronic kidney disease. Receptor-interacting protein 3 (RIP3) is an important contributor in inducing programmed necrosis, representing a newly identified mechanism of cell death combining features of both apoptosis and necrosis. In our study, RIP3 was strongly expressed in mice with hyperuricemia. RIP3 deficiency attenuated hyperuricemia in mice, evidenced by reduced serum uric acid and creatinine and enhanced urinary uric acid and creatinine, as well as the improved histological alterations in renal sections...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Magaiver Andrade-Silva, Marcos Antônio Cenedeze, Luiz Augusto Perandini, Raphael José Ferreira Felizardo, Ingrid Mizuno Watanabe, Juan Sebastian Henao Agudelo, Ângela Castoldi, Giselle Martins Gonçalves, Clarice Silvia Taemi Origassa, Patricia Semedo, Meire Ioshie Hiyane, Orestes Foresto Neto, Denise Maria Avancini Costa Malheiros, Marlene Antonia Reis, Clarice Kazue Fujihara, Roberto Zatz, Alvaro Pacheco-Silva, Niels Olsen Saraiva Câmara, Danilo Candido de Almeida
Acute kidney injury (AKI) is considered an inflammatory disease in which Toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, this study aimed evaluate the specific participation of TLR2 and TLR4 molecules on development of cisplatin-induced AKI...
March 2, 2018: Clinical Science (1979-)
Jiawei Li, Long Li, Shuo Wang, Chao Zhang, Long Zheng, Yichen Jia, Ming Xu, Tongyu Zhu, Yi Zhang, Ruiming Rong
BACKGROUND: Ischemia-reperfusion injury (IRI) is one of the major causes of postoperative renal allograft dysfunction, which is mainly the result of proinflammatory reactions including inflammatory responses, oxidative stress, and metabolic disorders. Resveratrol (RSV) plays an important role in protecting various organs in IRI because it reduces oxidative stress, lessens the inflammatory response, and exerts anti-apoptotic effects. The aim of this study was to demonstrate the renoprotective effect of RSV in inhibiting inflammatory responses, reducing oxidative stress, and decreasing cell apoptosis in vivo and in vitro...
February 22, 2018: Cellular Physiology and Biochemistry
Caren C Grabulosa, Silvia R Manfredi, Maria E Canziani, Beata M R Quinto, Rodrigo B Barbosa, Jacqueline F Rebello, Marcelo C Batista, Miguel Cendoroglo, Maria A Dalboni
TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry...
February 23, 2018: Experimental Cell Research
Jianxin Yang, Malou L H Snijders, Geert W Haasnoot, Cees van Kooten, Marko Mallat, Johan W de Fijter, Marian C Clahsen-van Groningen, Frans H J Claas, Michael Eikmans
BACKGROUND: Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome. METHODS: A total of 19 genes, including Toll like receptors (TLRs), complement components and regulators, and apoptosis-related genes were analyzed at the mRNA level by qPCR in 123 biopsies with acute rejection and paired pre-transplantation tissue (n = 75)...
February 20, 2018: Transplant Immunology
Salma Mukhtar Mir, Halley Gora Ravuri, Raj Kumar Pradhan, Sairam Narra, Jerald Mahesh Kumar, Madhusudana Kuncha, Sanjit Kanjilal, Ramakrishna Sistla
Sepsis-induced acute kidney injury (AKI) is responsible for 70-80% mortality in intensive care patients due to elevated levels of endotoxin, Lipopolysaccharide (LPS) caused by gram-negative infections. Ferulic acid (FA), a phenolic phytochemical is known for its renal protection on various induced models of nephrotoxicity. However, the curative effect of FA in LPS-induced AKI is not well studied. This study aimed to investigate the effect of FA on LPS-induced AKI in mice model and to understand the protective mechanisms involved, to provide evidence for FA in the treatment of AKI...
February 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mo Chen, Xiaoyong Lu, Ci Lu, Ning Shen, Yujie Jiang, Menglu Chen, Huaxiang Wu
BACKGROUND: In addition to the kidney, the intestine is one of the most important organs involved in uric acid excretion. However, the mechanism of urate excretion in the intestine remains unclear. Therefore, the relationship between soluble uric acid and the gut excretion in human intestinal cells was explored. The relevant signaling molecules were then also examined. METHODS: HT-29 and Caco-2 cell lines were stimulated with soluble uric acid. Western blotting and qRT-PCR were used to measure protein and mRNA levels...
February 7, 2018: Arthritis Research & Therapy
Yu Jiali, Da Jingjing, Dong Rong, Sun Yi, Nie Yingjie, Yu Fuxun, Zuo Lima, Zha Yan
contribution of high mobility group nucleosome-binding protein 1 (HMGN1)/ Toll-like receptor 4 (TLR4) pathway in diabetic nephropathy (DN). And as an intervention of the potential mechanism above, the insulin growth factor 1 receptor (IGF-1R) inhibitor was examined for its therapeutic effect in the diabetic mice. METHOD: Male C57BL/6J mice were administered streptozotocin(STZ) to induce diabetes and thus divided into 5 groups: the untreated group (DN group), the benazepril-treated group (BEN-DN group), the insulin-treated group (INS-DN group) and the IGF-1R inhibitor-treated group (IGF-DN group)...
January 30, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Waldemar Gozdzik, Stanisław Zielinski, Marzena Zielinska, Kornel Ratajczak, Piotr Skrzypczak, Sylwia Rodziewicz, Andrzej Kübler, Kalle Löfström, Piotr Dziegiel, Mateusz Olbromski, Barbara Adamik, Stanislaw Ryniak, Piotr Harbut, Johanna Albert, Claes Frostell
This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia-reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis...
January 2018: International Journal of Immunopathology and Pharmacology
Bo Liu, Fengxia Ding, Dong Hu, Yu Zhou, Chunlan Long, Lianju Shen, Yuanyuan Zhang, Deying Zhang, Guanghui Wei
BACKGROUND: Renal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis. METHODS: Renal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO)...
January 12, 2018: Stem Cell Research & Therapy
Shereen Saeid Elshaer, Hend Mohamed Anwar
Proximal tubule protein take-up is interceded by 2 receptors, megalin and cubilin. These receptors rescue an assortment of filtered ligands including fundamental vitamins and hormones. The objective of this study was to investigate the potential relation of megalin receptor injury with nuclear factor-kappa B (NF-κB) upregulation in acute kidney injury rat model. Twenty four rats were allocated into two groups: control group received saline, while the second group was intoxicated with cadmium chloride (2.4 mg Cd/kg/day i...
December 29, 2017: Journal of Biochemical and Molecular Toxicology
Yuji Nozaki, Shoichi Hino, Jinhai Ri, Kenji Sakai, Yasuaki Nagare, Mai Kawanishi, Kaoru Niki, Masanori Funauchi, Itaru Matsumura
The proinflammatory cytokine interleukin (IL)-18 is an important mediator of the organ failure induced by endotoxemia. IL-18 (known as an interferon-gamma (IFN-γ) inducing factor), and other inflammatory cytokines have important roles in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). We investigated the effect of inflammatory cytokines and Toll-like receptor 4 (TLR4) expression, an event that is accompanied by an influx of monocytes, including CD4⁺ T cells and antigen-presenting cells (APCs) in IL-18Rα knockout (KO) mice and wild-type (WT) mice after LPS injection...
December 20, 2017: International Journal of Molecular Sciences
Amy G Clark, Elizabeth S Buckley, Mary H Foster
Systemic lupus erythematosus is a debilitating autoimmune disease in which autoantibodies and autoreactive T cells destroy kidneys and other organs. Disease is clinically and genetically heterogeneous, suggesting that underlying mechanisms vary between patients. We previously used an autoantibody transgenic mouse reporter system to examine the effect of different autoimmune backgrounds on B-cell tolerance, failure of which is a fundamental defect in lupus. We identified a defect consistent with reversible anergy induced by endotoxin stimulation of B cells from Ig transgenic New Zealand Black (NZB) mice...
December 18, 2017: European Journal of Immunology
Hong Zhang, Ru Zhang, Juan Chen, Min Shi, Wei Li, Xiangcheng Zhang
BACKGROUND/AIMS: High mobility group box 1 (HMGB1) is an important mediator of the inflammatory response. It has been implicated in the pathogenesis of autoimmune diseases, atherosclerosis, and obesity. However, the effects of HMGB1 on diabetic nephropathy remain unclear. Here, we investigated the potential roles and mechanisms of an HMGB1 inhibitor, glycyrrhizic acid (GA), in renal injury with the streptozotocin (STZ)-induced rat model. METHODS: The diabetic rat was generated by intraperitoneal injection of STZ and then treated with the HMGB1 inhibitor GA or saline for 8 weeks...
November 15, 2017: Kidney & Blood Pressure Research
Xuxiang Sheng, Xiaoyan Zuo, Xihui Liu, Yang Zhou, Xia Sun
PURPOSE: IgA nephropathy (IgAN) is an immune complex-mediated disease involved in the kidney disease. Recent studies have revealed that Notch signaling-related genes are aberrantly expressed in various cell types and maybe associate with inflammation-induced carcinogenesis. The aim of our study was to investigate the function of Notch1 in the inflammatory response of IgAN. METHODS: The expression of Notch1, Jagged1 and NICD1 in 52 IgAN renal tissues and 20 control renal tissues was first determined using quantitative real-time PCR and Western blot...
December 11, 2017: International Urology and Nephrology
Daohai Zhang, Xianjin Bi, Yong Liu, Yinghui Huang, Jiachuan Xiong, Xinli Xu, Tangli Xiao, Yanlin Yu, Wei Jiang, Yunjian Huang, Jingbo Zhang, Bo Zhang, Jinghong Zhao
BACKGROUND/AIMS: Hyperphosphatemia is one of the most notable features of chronic kidney disease (CKD). Numerous epidemiological and clinical studies have found that high serum phosphate concentrations are associated with calcification in the coronary arteries. However, the mechanisms underlying the vascular calcification induced by high phosphate have not been understood fully. METHODS: Vascular smooth muscle cells (VSMCs) were cultured in high-phosphate media to induce vascular calcification, which was detected by Alizarin red S staining...
2017: Kidney & Blood Pressure Research
Jushuang Li, Liping Bao, Dongqing Zha, Lian Zhang, Ping Gao, Juan Zhang, Xiaoyan Wu
Inflammation plays a pivotal role in the development and progression of diabetic nephropathy (DN). Oridonin (Ori), a component isolated from Rabdosia rubescens, possesses remarkable anti-inflammatory, immunoregulatory and antitumor properties. However, the renoprotective effects of Ori and the underlying molecular mechanisms have not been explored in DN. In this study, we aimed to investigate the protective effects and potential mechanisms responsible for the anti-inflammatory effects of Ori in diabetes-induced renal injury in vivo and in vitro...
February 2018: International Immunopharmacology
Yong Zhou, Yin-Lu Ding, Jian-Liang Zhang, Peng Zhang, Jin-Qing Wang, Zhao-Hua Li
The non-alcoholic fatty liver disease (NAFLD) has become a serious medical problem and an increasing threat to public health. It is characterized by the abnormal fat accumulation in liver without excessive alcohol intake. The concurrent NAFLD might up-regulate the risk of chronic kidney disease as well as the mortality rate. Though various drugs have been investigated to attenuate NAFLD, further study is still necessary to find new therapeutic strategy and to reveal the underlying molecular mechanism. In the present study, NAFLD animal models were induced by feeding with high fat (HF) diet for 8 weeks...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hyun Su Choi, Jeong Kye Hwang, Jeong Goo Kim, Hyeon Seok Hwang, Sang Ju Lee, Yoon Kyung Chang, Ji Il Kim, In Sung Moon
Purpose: The aim of the present study was to investigate the protective effects of ischemic preconditioning for different periods of time and to elucidate the optimal safe ischemic preconditioning time for renal ischemia-reperfusion (I/R) injury in mice. Methods: A total of 25 male C57BL/6 mice were randomly divided into 5 groups (sham, I/R, ischemic preconditioning [IP]-3, IP-5, and IP-7 groups), in which the kidney was preconditioned with IP of various durations and then subjected to I/R injury (the last 3 groups)...
October 2017: Annals of Surgical Treatment and Research
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