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TLR4 KIDNEY

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https://www.readbyqxmd.com/read/28641285/role-of-glycyrrhizin-in-the-reduction-of-inflammation-in-diabetic-kidney-disease
#1
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
#2
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...
June 14, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28616865/isoacteoside-a-dihydroxyphenylethyl-glycoside-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization
#3
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 (ISO) 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 ISO is not completely understood. In this study, its anti-inflammatory mechanism in mouse macrophages was elucidated. EXPERIMENTAL APPROACH: The expression of the NF-κB pathway, MAPK pathway, iNOS, TNF-α, IL-6 and IL-1β was evaluated using western blotting, qRT-PCR or ELISA...
June 14, 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
#4
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-slows-down-age-related-kidney-disease-in-mice
#5
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...
June 8, 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
#6
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
#7
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 non-peptide TLR2 antagonists, C11 and C13, through pharmacophore-based virtual screening. At 10 μM, the level of interleukin-8 inhibition by C13 and C11 in human embryonic kidney TLR2 overexpressing cells is comparable to the commercially available TLR2 inhibitor CU-CPT22. In addition, C11 and C13 act in mouse macrophage-like RAW 264...
June 1, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28562479/sepsis-up-regulates-cd14-expression-in-a-myd88-dependent-and-trif-independent-pathway
#8
Zhixia Chen, Zhenzhen Shao, Shuya Mei, Zhengzheng Yan, Xibing Ding, Timothy Billiar, Quan Li
An overwhelming immune response, particularly from macrophages, plays a critical role in survival and organ damage in sepsis patients. TLRs are important receptors to recognize the conserved motifs expressed by invading bacteria. The TLRs except TLR3 signal via a MyD88 dependent pathway. TLR3 uses a TRIF dependent pathway, while TLR4 uses both MyD88 and TRIF dependent pathways. Previous studies indicated that CD14 was necessary for TLRs dependent production of pro-inflammatory cytokines. Blocking CD14 protected against the deleterious systemic inflammatory response associated with sepsis...
May 29, 2017: Shock
https://www.readbyqxmd.com/read/28544543/acute-toll-like-receptor-4-activation-impairs-rat-renal-microvascular-autoregulatory-behaviour
#9
Justin P Van Beusecum, Shali Zhang, Anthony K Cook, Edward W Inscho
AIM: Little is known about how toll-like receptor 4 (TLR4) influences the renal microvasculature. We hypothesized that acute TLR4 stimulation with lipopolysaccharide (LPS) impairs afferent arteriole autoregulatory behaviour, partially through reactive oxygen species (ROS). METHODS: We assessed afferent arteriole autoregulatory behaviour after LPS treatment (1 mg kg(-1) ; i.p.) using the in vitro blood perfused juxtamedullary nephron preparation. Autoregulatory behaviour was assessed by measuring diameter responses to step-wise changes in renal perfusion pressure...
May 25, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28542370/upregulation-of-tlr4-via-pkc-activation-contributes-to-impaired-wound-healing-in-high-glucose-treated-kidney-proximal-tubular-cells
#10
Jianping Peng, Hang Zheng, Xia Wang, Zhixiang Cheng
Acute kidney injury (AKI) leads to a worse prognosis in diabetic patients compared with prognoses in non-diabetic patients, but whether and how diabetes affects kidney repair after AKI remains unknown. Here, we used scratch-wound healing and transwell migration models to examine whether and how wound healing is affected by high glucose levels in cultured kidney proximal tubular cells (RPTC). The results show that scratch-wound healing and transwell migration were significantly slower in high-glucose-treated kidney tubular cells (30 mM glucose) than in low-glucose-treated cells (5...
2017: PloS One
https://www.readbyqxmd.com/read/28536433/a-new-model-of-self-resolving-leptospirosis-in-mice-infected-with-a-strain-of-leptospira-interrogans-serovar-autumnalis-harboring-lps-signaling-only-through-tlr4
#11
Bili Xia, Le Sun, Xia Fan, Haihan Xiao, Yongzhang Zhu, Jinhong Qin, Chengsong Cai, Wei Zhao, Yung-Fu Chang, Yan Zhang, Xiaokui Guo, Ping He
Leptospirosis is an emerging worldwide zoonosis caused by pathogenic Leptospira spp. Our understanding of leptospirosis pathogenesis and host immune response remains limited, while mechanistic studies are hindered by a lack of proper animal models and immunological reagents. Here we established a murine model of acute and self-resolving leptospirosis by infecting 10-week-old C57BL/6 mice with Leptospira interrogans serovar Autumnalis strain 56606v, with characteristic manifestations including jaundice as well as subcutaneous and pulmonary bleeding, but no kidney lesions...
May 24, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28485782/nac-attenuates-adriamycin-induced-nephrotic-syndrome-in-rats-through-regulating-tlr4-signaling-pathway
#12
H Yao, Z-Y Cai, Z-X Sheng
OBJECTIVE: Nephrotic syndrome (NS) is a detrimental renal disease that affects a large population. It is suggested that Toll-like Receptor 4 (TLR4) signaling pathway plays an important role in NS. The aim of this study was to evaluate the immunosuppressive effect of N-acetylcysteine (NAC) in the treatment of NS elucidate its interaction with TLR4 pathway in a rat model. MATERIALS AND METHODS: Rat NS model was constructed using the Bertain method by injecting adriamycin (4...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28485325/lipopolysaccharide-stimulates-surfactant-protein-a-in-human-renal-epithelial-hk-2-cells-through-upregulating-toll-like-receptor-4-dependent-mek1-2-erk1-2-nf-%C3%AE%C2%BAb-pathway
#13
Jiao Liu, Guang Li, Wen-Jie Xie, Lu Wang, Rui Zhang, Ke-Sheng Huang, Qing-Shan Zhou, De-Chang Chen
BACKGROUND: Surfactant protein-A (SP-A) contributes to the regulation of sepsis-induced acute kidney injury. In a previous study, we demonstrated that the expression of SP-A in the human renal tubular epithelial (HK-2) cells can be stimulated by lipopolysaccharide (LPS). The present study evaluated the possible signal-transducing mechanisms of LPS-induced SP-A biosynthesis in the HK-2 cells. METHODS: Tetrazolium salt colorimetry (MTT) assay was used to detect cell viability of HK-2 cells after LPS stimulation on different time points...
May 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28472797/up-regulation-of-hmgb1-exacerbates-renal-ischemia-reperfusion-injury-by-stimulating-inflammatory-and-immune-responses-through-the-tlr4-signaling-pathway-in-mice
#14
Chuan-Bao Chen, Long-Shan Liu, Jian Zhou, Xiao-Ping Wang, Ming Han, Xing-Yuan Jiao, Xiao-Shun He, Xiao-Peng Yuan
BACKGROUND/AIMS: The aim of this study was to elucidate how high-mobility group box 1 (HMGB1) exacerbates renal ischemic-reperfusion injury (IRI) by inflammatory and immune responses through the toll-like receptor 4 (TLR4) signaling pathway. METHODS: A total of 30 wild-type (WT) mice and 30 TLR4 knockout (TLR4-/-) mice were selected and then randomly assigned to the Sham, I/R or HMGB1 groups. The serum and kidney tissues of all mice were collected 24 h after the perfusion...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28466227/protective-effects-and-mechanisms-of-shenhua-tablet-on-toll-like-receptors-in-rat-model-of-renal-ischemia-reperfusion-injury
#15
Qing-Ping Li, Ri-Bao Wei, Xi Yang, Xiao-Yong Zheng, Ting-Yu Su, Meng-Jie Huang, Zhong Yin, Xiang-Mei Chen
OBJECTIVES: To investigate the protective effects and potential mechanisms of Shenhua Tablet (, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI). METHODS: Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg(-1)•d(-1)), low- and high-dose SHT (1.5 and 3.0 g•kg(-1)•d(-1), repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models...
May 3, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28423002/human-sr-bii-mediates-saa-uptake-and-contributes-to-saa-pro-inflammatory-signaling-in-vitro-and-in-vivo
#16
Irina N Baranova, Ana C P Souza, Alexander V Bocharov, Tatyana G Vishnyakova, Xuzhen Hu, Boris L Vaisman, Marcelo J Amar, Zhigang Chen, Alan T Remaley, Amy P Patterson, Peter S T Yuen, Robert A Star, Thomas L Eggerman
Serum amyloid A (SAA) is an acute phase protein with cytokine-like and chemotactic properties, that is markedly up-regulated during various inflammatory conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This study provides new evidence that SR-BII, splice variant of SR-BI, could function as an SAA receptor mediating its uptake and pro-inflammatory signaling. The uptake of Alexa Fluor488 SAA was markedly (~3 fold) increased in hSR-BII-expressing HeLa cells when compared with mock-transfected cells...
2017: PloS One
https://www.readbyqxmd.com/read/28416741/relaxin-abrogates-renal-interstitial-fibrosis-by-regulating-macrophage-polarization-via-inhibition-of-toll-like-receptor-4-signaling
#17
Lei Chen, Ming-Lei Sha, Deng Li, Yi-Ping Zhu, Xing-Jie Wang, Chen-Yi Jiang, Shu-Jie Xia, Yi Shao
Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit the CKD process, it is important to prevent renal fibrosis, though CKD remains incurable. Renal fibrosis can be inhibited by relaxin in several experimental models, but the mechanism of relaxin for antifibrotic potential is still not clear. And here we have studied the role of relaxin in macrophage polarization and renal inflammation after unilateral ureteral obstruction (UUO). Our results show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling, shift macrophage polarization toward the M2 phenotype and ameliorat renal fibrosis in the early stages of UUO...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28346614/crosstalk-between-transforming-growth-factor-beta-2-and-toll-like-receptor-4-in-the-trabecular-meshwork
#18
Humberto Hernandez, Wanda E Medina-Ortiz, Tomi Luan, Abbot F Clark, Colleen M McDowell
Purpose: The trabecular meshwork (TM) is involved in the outflow of aqueous humor and intraocular pressure (IOP) regulation. Regulation of the extracellular matrix (ECM) by TGFβ2 signaling pathways in the TM has been extensively studied. Recent evidence has implicated toll-like receptor 4 (TLR4) in the regulation of ECM and fibrogenesis in liver, kidney, lung, and skin. Here, we investigated the role of TGFβ2-TLR4 signaling crosstalk in the regulation of the ECM in the TM and ocular hypertension...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28330785/the-interplay-between-angiotensin-ii-tlr4-and-hypertension
#19
REVIEW
Vinicia Campana Biancardi, Gisele Facholi Bomfim, Wagner Luis Reis, Sarah Al-Gassimi, Kenia Pedrosa Nunes
Hypertension is a multifactorial disease. Although a number of different underlying mechanisms have been learned from the various experimental models of the disease, hypertension still poses challenges for treatment. Angiotensin II plays an unquestionable role in blood pressure regulation acting through central and peripheral mechanisms. During hypertension, dysregulation of the Renin-Angiotensin System is associated with increased expression of pro-inflammatory cytokines and reactive oxygen species causing kidney damage, endothelial dysfunction, and increase in sympathetic activity, among other damages, eventually leading to decline in organ function...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28322341/angiotensin-ii-induces-kidney-inflammatory-injury-and-fibrosis-through-binding-to-myeloid-differentiation-protein-2-md2
#20
Zheng Xu, Weixin Li, Jibo Han, Chunpeng Zou, Weijian Huang, Weihui Yu, Xiaoou Shan, Hazel Lum, Xiaokun Li, Guang Liang
Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2(-/-) mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice...
March 21, 2017: Scientific Reports
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