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Heiko Roedig, Madalina V Nastase, Helena Frey, Kristin Moreth, Jinyang Zeng-Brouwers, Chiara Poluzzi, Louise Tzung-Harn Hsieh, Christian Brandts, Simone Fulda, Malgorzata Wygrecka, Liliana Schaefer
Sterile inflammation is a therapeutic target in many diseases where it represents an important initiator of disease progression. However, the detailed mechanisms underlying its evolution and biological relevance are not yet completely elucidated. Biglycan, a prototype extracellular matrix-derived damage-associated molecular pattern, mediates sterile inflammation in macrophages through Toll-like receptor (TLR) 2 and/or TLR4-dependent signaling pathways. Here we discovered that soluble biglycan is a novel high-affinity ligand for CD14, a well-known GPI-anchored co-receptor for TLRs...
May 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Panpan Han, Sisi Wang, Qihuan Zhang, Shuhuan Zhang, Rong Shao, Wei Xu, Wenbing Zhang, Qiaoqing Xu, Qiwei Wei, Zhitao Qi
Toll-like receptors (TLRs) are important pattern recognition receptors (PRRs) of teleost innate immune system. However, information about TLRs is absent in Dabry's sturgeon (Acipenser dabryanus), one of the most primitive actinopterygii species. In the present study, the full lengths of adaTLR1 and adaTLR4 were cloned from Dabry's sturgeon using RT-PCR and RACE-PCR. The obtained adaTLR1 was 2957 bp in length, encoding a putative protein of 767 amino acids and adaTLR4 cDNA was 2902 bp in length, encoding a putative protein of 830 aa...
May 10, 2018: Developmental and Comparative Immunology
Hong Lu, Lianfeng Wu, Leping Liu, Qingqing Ruan, Xing Zhang, Weilong Hong, Shijia Wu, Guihua Jin, Yongheng Bai
Interstitial inflammation is the main pathological feature in kidneys following injury, and the polarization of macrophages is involved in the process of inflammatory injury. Previous studies have shown that quercetin has a renal anti-inflammatory activity, but the potential molecular mechanism remains unknown. In obstructive kidneys, administration of quercetin inhibited tubulointerstitial injury and reduced the synthesis and release of inflammatory factors. Further study revealed that quercetin inhibited the infiltration of CD68+ macrophages in renal interstitium...
May 10, 2018: Biochemical Pharmacology
Alessandra Tammaro, Sandrine Florquin, Mascha Brok, Nike Claessen, Loes M Butter, Gwendoline J D Teske, Onno J de Boer, Thomas Vogl, Jaklien C Leemans, Mark C Dessing
Despite advances in our understanding of the mechanisms underlying progression of chronic kidney disease and the development of fibrosis, only limited efficacious therapies exist. The calcium binding protein S100A8/A9, is a damage-associated molecular pattern which can activate TLR4 or RAGE. Activation of these receptors is involved in the progression of renal fibrosis, however the role of S100A8/A9 herein remains unknown. Therefore, we analyzed S100A8/A9 expression in patients and mice with obstructive nephropathy and subjected wild-type and S100A9 KO mice lacking the heterodimer S100A8/A9 to Unilateral Ureteral Obstruction (UUO)...
May 10, 2018: Clinical and Experimental Immunology
Yujiao Guo, Meng Wang, Jingyi Mou, Zhi Zhao, Juan Yang, Fengming Zhu, Guangchang Pei, Han Zhu, Yuxi Wang, Gang Xu, Rui Zeng, Ying Yao
Cisplatin is a commonly used chemotherapeutic agent in the treatment of different types of malignant tumors, but nephrotoxicity limits its usage. Therefore, in this study, we aimed to determine the possible protective effect of Huaiqihuang (HQH) extractum, a kind of Chinese herbal complex that consists of Trametes robiniophila Murr., Lycium barbarum and Polygonatum sibiricum, against nephrotoxicity induced by cisplatin in mice. We found that pretreatment with HQH significantly attenuated the cisplatin-induced increase in blood urea nitrogen (BUN), interstitial congestion, acute renal tubular injury and tubular cell apoptosis and necroptosis...
May 9, 2018: Scientific Reports
Bruns A Watts, Thampi George, Edward R Sherwood, David W Good
Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs HCO3 - absorption in the MTAL by: 1) decreasing the intrinsic HCO3 - absorptive capacity, and 2) enhancing inhibition of HCO3 - absorption by LPS through upregulation of TLR4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis...
May 9, 2018: American Journal of Physiology. Renal Physiology
Jianjun Xu, Caijiao Lu, Zhengjun Liu, Peng Zhang, Hailei Guo, Tingting Wang
Schizandrin B ( Sch B ) is the main component isolated from Schizandra fruit ( Schisandra chinensis ). While Sch B is established as having antioxidant, anti-proliferation and anti-inflammatory properties, but its activity in sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of Sch B in sepsis. Our experimental results demonstrated that Sch B inhibited production of IL-1β, TNF-α, IL-6 and HMGB1 by LPS-activated RAW264.7 cells. Moreover, Sch B suppressed expression of iNOS, reduced production of PGE2, blocked expression of MyD88 and TLR4, suppressed the activity of NF-κB and decreased phosphorylation of MAPKs in LPS-activated RAW264...
2018: American Journal of Translational Research
Rongzong Qiu, Weifeng Yao, Haocong Ji, Dongdong Yuan, Xiaofeng Gao, Weiping Sha, Fei Wang, Pinjie Huang, Ziqing Hei
BACKGROUND: Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. METHODS: The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups...
May 4, 2018: Life Sciences
Fangfang Bi, Fang Chen, Yanning Li, Ai Wei, Wangsen Cao
Renal anti-aging protein Klotho exhibits impressive properties of anti-inflammation and renal protection, however is suppressed early after renal injury, making Klotho restoration an attractive strategy of treating renal inflammatory disorders. Here, we reported that Klotho is enriched in macrophages and Klotho preservation by Rhein, an anthraquinone derived from medicinal plant rhubarb, attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation...
May 5, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Feng Han, Xin-Xin Xia, Meng Dou, Yu-Xiang Wang, Wu-Jun Xue, Xiao-Ming Ding, Jin Zheng, Chen-Guang Ding, Pu-Xun Tian
Arctigenin (ATG) is one of the main active substances in fruit derived from Arctium lappa L. Previous studies have reported that ATG have antitumor, neuroprotective, antioxidant, antifibrosis and anti-inflammatory functions. However, the actions of ATG in kidney with acute injury following ischemia/ reperfusion (I/R) is still uncertain. In our study, mice were subjected to kidney I/R by having the kidney pedicles clamped and administered with vehicle or ATG (1, 3 or 9 mg/kg/d) via oral gavage for 7 consecutive days prior to I/R...
April 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bingxing An, Jiangwei Xia, Tianpeng Chang, Xiaoqiao Wang, Jian Miao, Lingyang Xu, Lupei Zhang, Xue Gao, Yan Chen, Junya Li, Huijiang Gao
Cattle internal organs as accessible raw materials have a long history of being widely used in beef processing, feed and pharmaceutical industry. These traits not only are of economic interest to breeders, but they are intrinsically linked to many valuable traits, such as growth, health, and productivity. Using the Illumina Bovine HD 770K SNP array, we performed a genome-wide association study for heart weight (HW), liver weight (LIW), spleen weight (SW), lung weight (LUW) and kidney weight (KW) in 1217 Simmental cattle...
April 20, 2018: Physiological Genomics
Shue-Fen Luo, Chia-Yin Chin, Ling-Jun Ho, Wen-Yi Tseng, Chang-Fu Kuo, Jenn-Haung Lai
BACKGROUND: Renal disease is prevalent in gouty patients and monosodium urate (MSU) crystal deposition in the kidney can be detected in some gouty nephropathy patients. MSU crystals can induce inflammatory events, we investigated the MSU-induced expression of intercellular adhesion molecule (ICAM)-1 on human renal mesangial cells (HRMCs) and the involved signal transduction mechanisms. METHODS: The HRMCs cell line was purchased from ScienCell Research Laboratories...
January 31, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Hadeer O Abou-Hany, Hoda Atef, Eman Said, Hassan A Elkashef, Hatem A Salem
Renal Ischemia (RI) usually develops as a secondary manifestation of hypertension, various cardiovascular disorders and renal transplantation. It exerts hypoxic oxidative stress to kidneys, together with stimulation of several immune-mediated inflammatory cascades. Such events eventually damage renal tubules and glomeruli, driving acute kidney injury (AKI) and ultimately, renal failure. Crocin; the main bioactive constituent of Crocus sativus extract has been reported to demonstrate numerous pharmacological merits...
March 27, 2018: Environmental Toxicology and Pharmacology
Liping Zhu, Jiakai Han, Rongrong Yuan, Lei Xue, Wuyan Pang
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood. METHODS: The DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model...
March 31, 2018: Biological Research
Wen-Yang Wei, Hai-Tong Wan, Li Yu, Yi-Yu Lu, Yu He
To study the effect and underlying mechanism of Mahuang Tang against influenza A virus in vitro , the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods, and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER), median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang...
February 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Yunshan Guo, Jing Zhang, Xingqiang Lai, Miaojuan Chen, Yunshan Guo
T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) as a member of immunoglobulin superfamily, has been shown to play a crucial role in host adaptive immunity and tolerance. However, its role in kidney ischemia-reperfusion injury (IRI) remains unknown. In this study, we investigated the role and mechanism of Tim-3 signaling after kidney IRI. In an established murine model of kidney IRI, we found that Tim-3 expression is enhanced on monocytes/macrophages. Anti-Tim-3 Ab RMT3-23 ameliorates biochemical and histologic kidney injury, reduces apoptosis, decreases macrophage infiltration and cytokine production in ischemic kidneys...
March 23, 2018: Clinical and Experimental Immunology
Zhi Cao, Minping Zheng, Huifang Lv, Kangkang Guo, Yanming Zhang
The Toll-like receptors (TLRs) of the innate immune system provide the host with the ability to detect and respond to viral infections. The present study aimed to investigate the mRNA and protein expression levels of TLR2, 3, 4 and 7 in porcine tissues upon infection with the highly virulent Shimen strain of classical swine fever virus (CSFV). Reverse transcription‑quantitative polymerase chain reaction was used to detect the mRNA expression levels of CSFV and TLR, whereas western blotting was used to detect the expression levels of TLR proteins...
March 14, 2018: Molecular Medicine Reports
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...
May 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-)
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