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TLR4 KIDNEY

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https://www.readbyqxmd.com/read/28930914/the-protective-effect-of-a-short-peptide-derived-from-cold-inducible-rna-binding-protein-in-renal-ischemia-reperfusion-injury
#1
Joseph McGinn, Fangming Zhang, Monowar Aziz, Weng-Lang Yang, Jeffrey Nicastro, Gene F Coppa, Ping Wang
Extracellular cold-inducible RNA-binding protein (CIRP) functions as damage-associated molecular pattern (DAMP) and has been demonstrated to be responsible in part for the damage occurring after renal ischemia-reperfusion (I/R). A short peptide derived from CIRP, named C23, binds to myeloid differentiation factor 2 (MD2), a Toll-like receptor 4 (TLR4) co-receptor. We hypothesize that C23 reduces renal ischemia-reperfusion (RIR) injury by blocking CIRP. We observed that pre-treatment with C23 significantly decreased the levels of recombinant mouse CIRP-induced TNF-α in a dose-dependent fashion in cultured macrophages...
September 19, 2017: Shock
https://www.readbyqxmd.com/read/28898406/dc-sign-reacts-with-tlr4-and-regulates-inflammatory-cytokine-expression-via-nf-%C3%AE%C2%BAb-activation-in-renal-tubular-epithelial-cells-during-acute-renal-injury
#2
Danying Feng, Yanping Wang, Yan Liu, Liping Wu, Xiao Li, Yufan Chen, Yuanyuan Chen, Yafeng Chen, Chundi Xu, Ke Yang, Tong Zhou
In the pathological process of acute kidney injury (AKI), innate immune receptors are essential in inflammatory response modulation; however, the precise molecular mechanisms are still unclear. Our study sought to demonstrate the inflammatory response mechanisms in renal tubular epithelial cells via Toll-like receptor 4 (TLR4) and dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) signaling. We found that DC-SIGN exhibited strong expression in renal tubular epithelial cells of human acute renal injury tissues...
September 12, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28854431/involvement-of-s100a8-a9-tlr4-nlrp3-inflammasome-pathway-in-contrast-induced-acute-kidney-injury
#3
Xuexian Tan, Xiaohe Zheng, Zena Huang, Jiaqiong Lin, Chuli Xie, Yan Lin
BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. METHODS: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI...
August 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28836571/pharmacological-inhibition-of-macrophage-toll-like-receptor-4-nuclear-factor-kappa-b-alleviates-rhabdomyolysis-induced-acute-kidney-injury
#4
Rong-Shuang Huang, Jiao-Jiao Zhou, Yu-Ying Feng, Min Shi, Fan Guo, Shen-Ju Gou, Stephen Salerno, Liang Ma, Ping Fu
BACKGROUND: Acute kidney injury (AKI) is the most common and life-threatening systemic complication of rhabdomyolysis. Inflammation plays an important role in the development of rhabdomyolysis-induced AKI. This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role of macrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. METHODS: C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis, and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0...
August 21, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28822965/diabetes-increases-the-susceptibility-to-acute-kidney-injury-after-myocardial-infarction-through-augmented-activation-of-renal-toll-like-receptors-in-rats
#5
Kouhei Ohno, Atsushi Kuno, Hiromichi Murase, Shingo Muratsubaki, Takayuki Miki, Masaya Tanno, Toshiyuki Yano, Satoko Ishikawa, Tomohisa Yamashita, Tetsuji Miura
Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined roles of renal toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in OLETF, a rat DM model, and LETO, non-diabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and MyD88 were significantly higher in sham-operated OLETF than in sham-operated LETO, though levels of TLR1, TLR3, and TRL4 were similar...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28817116/total-tanshinones-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization-via-the-myd88-pathway
#6
Hongwei Gao, Xin Liu, Wen Sun, Naixin Kang, Yanli Liu, Shilin Yang, Qiong-Ming Xu, Chunming Wang, Xiuping Chen
Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-α, IL-6, and IL-1β in RAW264...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28805489/atorvastatin-attenuates-experimental-contrast-induced-acute-kidney-injury-a-role-for-tlr4-myd88-signaling-pathway
#7
Rongzheng Yue, Chuan Zuo, Jing Zeng, Baihai Su, Ye Tao, Songmin Huang, Rui Zeng
OBJECTIVES: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28764846/uric-acid-promotes-vascular-stiffness-maladaptive-inflammatory-responses-and-proteinuria-in-western-diet-fed-mice
#8
Annayya R Aroor, Guanghong Jia, Javad Habibi, Zhe Sun, Francisco I Ramirez-Perez, Barron Brady, Dongqing Chen, Luis A Martinez-Lemus, Camila Manrique, Ravi Nistala, Adam T Whaley-Connell, Vincent G Demarco, Gerald A Meininger, James R Sowers
OBJECTIVE: Aortic vascular stiffness has been implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese individuals. However, the mechanism promoting these adverse effects are unclear. In this context, promotion of obesity through consumption of a western diet (WD) high in fat and fructose leads to excess circulating uric acid. There is accumulating data implicating elevated uric acid in the promotion of CVD and CKD. Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with allopurinol would prevent a rise in vascular stiffness and proteinuria in a translationally relevant model of WD-induced obesity...
September 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28743964/toll-like-receptor-4-deficiency-reduces-oxidative-stress-and-macrophage-mediated-inflammation-in-hypertensive-kidney
#9
Sathnur Pushpakumar, Lu Ren, Sourav Kundu, Alejandra Gamon, Suresh C Tyagi, Utpal Sen
Oxidative stress and inflammation are integral to hypertension-induced renal injury. A unifying feature for the two components is Toll-like receptors (TLR), which are key regulators of the innate immune system. Recent studies implicate TLR4 activation and oxidative stress in cardiovascular diseases and also as a link between inflammation and hypertension. However, its role in hypertension induced renal injury remains unexplored. In the present study, we investigated whether TLR-4 deficiency reduces Ang-II-induced renal injury and fibrosis by attenuating reactive oxygen species (ROS) production and inflammation...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28734896/porcine-cd14-gene-silencing-partially-inhibited-the-bacterial-immune-response-mediated-by-tlr4-signaling-pathway
#10
Chaohui Dai, Haifei Wang, Guoqiang Zhu, Shenglong Wu, Wenbin Bao
Cluster of differentiation antigen 14 (CD14) is the membrane receptor protein in Toll-like Receptor 4 (TLR4) signaling pathway, which plays an important regulation role in not only innate immune response but also adaptive immune response. In this study, the pig kidney epithelial cell (PK15) line with CD14 gene silencing mediated by lentivirus was established and cells of CD14-RNAi and NC group were exposed to three kinds of Escherichia coli (E. coli F18ab, E. coli F18ac and E. coli K88ac) and LPS. Then qPCR and western blot were used to detect expression levels of TLR4 signaling pathway-related genes...
July 19, 2017: Gene
https://www.readbyqxmd.com/read/28706136/swine-irf3-irf7-attenuates-inflammatory-responses-through-tlr4-signaling-pathway
#11
Pei-Ge Chen, Yan-Jing Guan, Guang-Ming Zha, Xian-Qin Jiao, He-Shui Zhu, Cheng-Yu Zhang, Yue-Ying Wang, He-Ping Li
To explore the role of IRF3/IRF7 during inflammatory responses, we investigated the effects of swine IRF3/IRF7 on TLR4 signaling pathway and inflammatory factors expression in porcine kidney epithelial PK15 cell lines. We successfully constructed eukaryotic vectors PB-IRF3 and PB-IRF7, transfected these vectors into PK15 cells and observed GFP under a fluorescence microscope. In addition, RT-PCR was also used to detect transfection efficiency. We found that IRF3/IRF7 was efficiently overexpressed in PK15 cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28685413/telluric-acid-ameliorates-endotoxemic-kidney-injury-in-mice-involvement-of-tlr4-nrf2-and-pi3k-akt-signaling-pathways
#12
Ahmed F Mohamed, Marwa M Safar, Hala F Zaki, Helmy M Sayed
Being one of the most abundant trace elements in the human body, the therapeutic potential of tellurium-based compounds has been a target of interest. Recent reports denoted their redox-modulating and anti-inflammatory activities in experimental endotoxemia. However, their potential nephroprotective effect against endotoxemic kidney injury is yet to be elucidated. This study investigated the possible renoprotective effect of telluric acid (TEL) against lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, targeting toll-like receptor 4 (TLR4), phosphoinositide 3-kinase (PI3K)/Akt, and nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways as possible mechanistic contributors to TEL's effect...
July 6, 2017: Inflammation
https://www.readbyqxmd.com/read/28655852/role-of-esat-6-in-renal-injury-by-regulating-microrna-155-expression-via-tlr4-myd88-signaling-pathway-in-mice-with-mycobacterium-tuberculosis-infection
#13
Zhong-Qi Zhou, Zhi-Kui Wang, Lei Zhang, Yue-Qin Ren, Zhong-Wei Ma, Nan Zhao, Fu-Yun Sun
The study aims to investigate the underlying mechanism involved in the early secretory antigenic target-6 (ESAT-6) in renal injury through regulation of the expression of miR-155 through the oll-like receptor (TLR)-4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway in Mycobacterium tuberculosis (MTB)-infected mice. Sixty C57BL/6 mice with MTB-induced renal injury were randomly assigned into control, MTB, mimic, inhibitor, inhibitor + ESAT6, and inhibitor + ESAT6 + TAK242 groups. Body weight, the ratio of kidney weight to body weight (Kw/Bw), blood urea nitrogen (BUN), and serum creatinine (Scr) of mice were measured...
August 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28641285/role-of-glycyrrhizin-in-the-reduction-of-inflammation-in-diabetic-kidney-disease
#14
Vikram Thakur, Syeda Nargis, Mayra Gonzalez, Swetak Pradhan, Daniel Terreros, Munmun Chattopadhyay
BACKGROUND: Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes. Recent evidence suggests chronic inflammation to be one of the causal factors of DKD. The mechanisms entailed are not completely elucidated except that a variety of cytokines play a major role in this process. High mobility group box 1 (HMGB1) is a pro-inflammatory toll-like receptor-4 (TLR4)-binding cytokine that is involved in inflammation-associated gene expression. This investigation was designed to assess the involvement of HMGB1, TLR-4, and nuclear factor (NF)-κB in the development of DKD and to evaluate that whether blocking HMGB1 by its natural inhibitor Glycyrrhizin (GLC) can reduce the progression of the disease...
June 23, 2017: Nephron
https://www.readbyqxmd.com/read/28623542/identification-of-differentially-expressed-mirnas-associated-with-chronic-kidney-disease-mineral-bone-disorder
#15
Kyung Im Kim, Sohyun Jeong, Nayoung Han, Jung Mi Oh, Kook-Hwan Oh, In-Wha Kim
The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease (CKD) to predict putative microRNA (miRNA) in CKD-mineral bone disorder (CKD-MBD) and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD-MBD was determined...
September 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28616865/isoacteoside-a-dihydroxyphenylethyl-glycoside-exhibits-anti-inflammatory-effects-through-blocking-toll-like-receptor-4-dimerization
#16
Hongwei Gao, Yankun Cui, Naixin Kang, Xin Liu, Yanli Liu, Yue Zou, Ziyu Zhang, Xiaoran Li, Shilin Yang, Ji Li, Chunming Wang, Qiong-Ming Xu, Xiuping Chen
BACKGROUND AND PURPOSE: Isoacteoside (is a phenylethanoid isolated from Monochasma savatieri Franch. ex Maxim., which is an anti-inflammatory herb widely used in traditional Chinese medicine. However, the exact mechanism of the anti-inflammatory activity of isoacteoside is not completely understood. In this study, its anti-inflammatory mechanism was elucidated in mouse macrophages. EXPERIMENTAL APPROACH: The expression of the NF-κB pathway, MAPK pathway, iNOS, TNF-α, IL-6 and IL-1β was evaluated using Western blotting, quantitative real-time PCR or ELISA...
September 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28600543/innate-and-adaptive-immunity-are-progressively-activated-in-parallel-with-renal-injury-in-the-5-6-renal-ablation-model
#17
Camilla Fanelli, Simone C A Arias, Flavia G Machado, Jessica K Okuma, Denise M A C Malheiros, Hatylas Azevedo, Carlos A Moreira-Filho, Niels O S Camara, Clarice K Fujihara, Roberto Zatz
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1β and NLRP3 were individually assessed...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596381/a-dual-agonist-of-farnesoid-x-receptor-fxr-and-the-g-protein-coupled-receptor-tgr5-int-767-reverses-age-related-kidney-disease-in-mice
#18
Xiaoxin X Wang, Yuhuan Luo, Dong Wang, Luciano Adorini, Mark Pruzanski, Evgenia Dobrinskikh, Moshe Levi
Even in healthy individuals, renal function gradually declines during aging. However, an observed variation in the rate of this decline has raised the possibility of slowing or delaying age-related kidney disease. One of the most successful interventional measures that slows down and delays age-related kidney disease is caloric restriction. We undertook the present studies to search for potential factors that are regulated by caloric restriction and act as caloric restriction mimetics. Based on our prior studies with the bile acid-activated nuclear hormone receptor farnesoid X receptor (FXR) and G protein-coupled membrane receptor TGR5 that demonstrated beneficial effects of FXR and TGR5 activation in the kidney, we reasoned that FXR and TGR5 could be excellent candidates...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28591009/surfactant-proteins-a-and-d-attenuate-lps-induced-apoptosis-in-primary-intestinal-epithelial-cells-iecs
#19
Linlin Zhang, Qinghe Meng, Natesh Yepuri, Guirong Wang, Xiuming Xi, Robert N Cooney
INTRODUCTION: SP-A/D KO mice with sepsis demonstrate more severe lung, kidney and gut injury/apoptosis than WT controls. We hypothesize SP-A and SP-D directly regulate LPS-induced P38 MAPK activation and gut apoptosis during sepsis. METHODS: Primary IECs were established from SP-A/D KO or C57BL/6 WT mice, stimulated with LPS and harvested at 24 h. IECs from WT mice were treated with SP-A, SP-D or vehicle for 20 h, then LPS for 24 h. Apoptosis, cleaved caspase-3 levels and the ratio of BAX/Bcl-2 were assayed...
June 6, 2017: Shock
https://www.readbyqxmd.com/read/28570013/toll-like-receptor-2-antagonists-identified-through-virtual-screening-and-experimental-validation
#20
Prasannavenkatesh Durai, Hyeon-Jun Shin, Asma Achek, Hyuk-Kwon Kwon, Rajiv Gandhi Govindaraj, Suresh Panneerselvam, Dhanusha Yesudhas, Jiwon Choi, Kyoung Tai No, Sangdun Choi
Toll-like receptor 2 (TLR2) antagonists are key therapeutic targets because they inhibit several inflammatory diseases caused by surplus TLR2 activation. In this study, we identified two novel nonpeptide TLR2 antagonists, C11 and C13, through pharmacophore-based virtual screening. At 10 μm, the level of interleukin (IL)-8 inhibition by C13 and C11 in human embryonic kidney TLR2 overexpressing cells was comparable to the commercially available TLR2 inhibitor CU-CPT22. In addition, C11 and C13 acted in mouse macrophage-like RAW 264...
June 1, 2017: FEBS Journal
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