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Toll-like Receptors

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https://www.readbyqxmd.com/read/29792782/25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-as-an-antiviral-and-immunomodulator-against-herpes-simplex-virus-1-infection-in-hela-cells
#1
Archit Kumar, Mini P Singh, Ragini S Kumar, Radha Kanta Ratho
The antiviral and immunomodulatory role of vitamin D has been shown in various viral infections. However, there is scanty literature available about the effect of vitamin D supplementation in herpes simplex virus-1 (HSV-1) infection. Therefore, the present study aimed to evaluate the role of two different forms of vitamin D: 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3) against HSV-1 in HeLa cells. The HeLa cells were supplemented with either 25D3 or 1,25D3 before HSV-1 infection and were studied after 6, 12, and 24 h postinfection (p...
May 24, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29791907/toll-like-receptor-3-signaling-contributes-to-regional-neutrophil-recruitment-in-cultured-human-glomerular-endothelial-cells
#2
Qiang Liu, Tadaatsu Imaizumi, Shogo Kawaguchi, Tomomi Aizawa, Tomoh Matsumiya, Shojiro Watanabe, Koji Tsugawa, Hidemi Yoshida, Kazushi Tsuruga, Kensuke Joh, Hiroshi Kijima, Hiroshi Tanaka
BACKGROUND: Given the importance of neutrophil recruitment in the pathogenesis of glomerulonephritis (GN), the representative neutrophil chemoattractant C-X-C motif chemokine 1 (CXCL1)/GROα and the adhesion molecule E-selectin in glomerular endothelial cells (GECs) play a pivotal role in the development of GN. Endothelial Toll-like receptor 3 (TLR3) is thought to be involved in the inflammatory response via innate immunity. However, the role of endothelial TLR3 signaling in the expression of neutrophil chemoattractants and adhesion molecules remains to be elucidated...
May 23, 2018: Nephron
https://www.readbyqxmd.com/read/29791868/ontogeny-of-white-matter-toll-like-receptor-expression-and-motor-skills-in-the-neonatal-ferret
#3
Jessica M Snyder, Thomas R Wood, Kylie Corry, Daniel H Moralejo, Pratik Parikh, Sandra E Juul
Inflammation caused by perinatal infection, superimposed with hypoxia and/or hyperoxia, appears to be important in the pathogenesis of preterm neonatal encephalopathy, with white matter particularly vulnerable during the third trimester. The associated inflammatory response is at least partly mediated through Toll-like receptor (TLR)-dependent mechanisms. Immunohistochemistry, gene expression, and behavioral studies were used to characterize white matter development and determine TLR3 and TLR4 expression and accumulation in the neonatal ferret brain...
May 20, 2018: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#4
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29791585/protective-effect-and-mechanism-of-lactobacillus-on-cerebral-ischemia-reperfusion-injury-in-rats
#5
Shi Wanchao, Ma Chen, Su Zhiguo, Xie Futang, Shi Mengmeng
The present study was designed to investigate the protective effects and mechanism of inactivated lactobacillus (ILA) on cerebral ischemia reperfusion injury (CIRI) in rats. In this experiment, 30 male Sprague Dawley rats were randomly divided into control group, IRI groups, and ILA group. A middle cerebral artery occlusion and reperfusion model was prepared. The rats were killed after 24 hours of recovery of blood flow of cerebral ischemia resulting from 60-min occlusion. The cerebral infarction volume and neurological scores were assayed by staining and behavioral observation...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29791566/cytidine-phosphate-guanosine-oligodeoxynucleotides-in-combination-with-cd40-ligand-decrease-periodontal-inflammation-and-alveolar-bone-loss-in-a-tlr9-independent-manner
#6
Qian Zhao, Yang Hu, Shu Deng, Pei Yu, Bowen Chen, Zuomin Wang, Xiaozhe Han
Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. OBJECTIVE: This study aimed to explore whether such effect is dependent on TLR9 signaling. MATERIAL AND METHODS: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses...
2018: Journal of Applied Oral Science: Revista FOB
https://www.readbyqxmd.com/read/29787749/epidermal-hmgb1-activates-dermal-fibroblasts-and-causes-hypertrophic-scar-formation-in-reduced-hydration
#7
Jingling Zhao, Jianxing Yu, Yingbin Xu, Lei Chen, Fei Zhou, Qiyi Zhai, Jun Wu, Bin Shu, Shaohai Qi
High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory reactions and is known to play a key role in tissue repair and fibrosis. However, the function of HMGB1 in fibrotic skin diseases, such as hypertrophic scar formation, remains unclear. In this study, HMGB1 was detected in the nuclei of epidermal cells in normal skin and had accumulated in the cytoplasm in hypertrophic scars. By establishing a keratinocyte-fibroblast co-culture and conditional medium treatment models, we found that a reduced hydration condition increased the expression and secretion of HMGB1 in keratinocytes, subsequently activating dermal fibroblasts...
May 19, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29787561/interplay-of-strain-and-race-ethnicity-in-the-innate-immune-response-to-m-tuberculosis
#8
P Nahid, L G Jarlsberg, M Kato-Maeda, M R Segal, D H Osmond, S Gagneux, K Dobos, M Gold, P C Hopewell, D M Lewinsohn
BACKGROUND: The roles of host and pathogen factors in determining innate immune responses to M. tuberculosis are not fully understood. In this study, we examined host macrophage immune responses of 3 race/ethnic groups to 3 genetically and geographically diverse M. tuberculosis lineages. METHODS: Monocyte-derived macrophages from healthy Filipinos, Chinese and non-Hispanic White study participants (approximately 45 individuals/group) were challenged with M. tuberculosis whole cell lysates of clinical strains Beijing HN878 (lineage 2), Manila T31 (lineage 1), CDC1551 (lineage 4), the reference strain H37Rv (lineage 4), as well as with Toll-like receptor 2 agonist lipoteichoic acid (TLR2/LTA) and TLR4 agonist lipopolysaccharide (TLR4/LPS)...
2018: PloS One
https://www.readbyqxmd.com/read/29787520/early-tlr4-blockade-attenuates-sterile-inflammation-mediated-stress-in-islets-during-isolation-and-promotes-successful-transplant-outcomes
#9
Charles A Chang, Kayla Murphy, Robert R Kane, Michael Lawrence, Bashoo Naziruddin
BACKGROUND: During the isolation process, pancreatic islets are exposed to an environment of sterile inflammation resulting in an upregulated inflammatory state prior to transplantation. Toll-like receptor 4 (TLR4) has been identified as a major mediator of sterile inflammation. Therefore, we sought to determine whether early TLR4 blockade would be effective in reducing the inflammatory burden in islets pretransplant. METHODS: Islets from C57BL/6 mice were treated with a TLR4 antagonist during the pancreatic ductal perfusion and digestion steps of the isolation process...
May 22, 2018: Transplantation
https://www.readbyqxmd.com/read/29786555/innate-immunity-in-stem-cell-derived-hepatocytes
#10
REVIEW
Lena Fischer, David C Hay, Cliona O'Farrelly
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784900/irak-inhibitor-protects-the-intestinal-tract-of-necrotizing-enterocolitis-by-inhibiting-the-toll-like-receptor-tlr-inflammatory-signaling-pathway-in-rats
#11
Yu Hou, Xin Lu, Yueju Zhang
BACKGROUND The aim of this study was to assess the effects of interleukin-1 (IL-1) receptor associated kinase (IRAK) inhibitors on intestinal injury induced by necrotizing enterocolitis (NEC) in neonatal rats and its regulation on the intestinal Toll-like receptor (TLR) inflammatory signaling pathway. MATERIAL AND METHODS The neonatal rat models of NEC were established though hypoxia-cold stimulation. All rats were divided into 3 groups: an NEC model group (NEC group), an IRAK inhibitor group (IRAKI group), and a normal control group (NC group)...
May 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29784886/-legionella-pneumophila-is-directly-sensitive-to-2-deoxyglucose-phosphate-via-its-uhpc-transporter-but-is-indifferent-to-shifts-in-host-cell-glycolytic-metabolism
#12
Jordan V Price, Kallie Jiang, Abigail Galantowicz, Alana Freifeld, Russell E Vance
Toll-like receptor stimulation induces a pronounced shift to increased glycolytic metabolism in mammalian macrophages. We observed that bone marrow-derived macrophages (BMMs) increase glycolysis in response to infection with Legionella pneumophila ( L. pneumophila ), but the role of host macrophage glycolysis on intracellular L. pneumophila replication is not currently understood. Treatment with 2-deoxyglucose (2DG) blocks L. pneumophila replication in mammalian macrophages but has no effect on bacteria grown in broth...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29784770/tlr-activated-repression-of-fe-s-cluster-biogenesis-drives-a-metabolic-shift-and-alters-histone-and-tubulin-acetylation
#13
Wing-Hang Tong, Nunziata Maio, De-Liang Zhang, Erika M Palmieri, Hayden Ollivierre, Manik C Ghosh, Daniel W McVicar, Tracey A Rouault
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29783985/the-doses-of-plasmid-backbone-plays-a-major-role-in-determining-the-hbv-clearance-in-hydrodynamic-injection-mouse-model
#14
Xian Wang, Jianmin Zhu, Yong Zhang, Yue Li, Tai Ma, Qun Li, Jiegou Xu, Long Xu
BACKGROUND: Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. METHODS: In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence...
May 21, 2018: Virology Journal
https://www.readbyqxmd.com/read/29782532/hepatitis-c-virus-ns4b-induces-the-degradation-of-trif-to-inhibit-tlr3-mediated-interferon-signaling-pathway
#15
Yisha Liang, Xuezhi Cao, Qiang Ding, Yanan Zhao, Zhenliang He, Jin Zhong
Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781535/mir-1178-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages-partly-via-tlr4
#16
Ge Shi, Guofeng Mao, Kejie Xie, Dongdong Wu, Wei Wang
Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR-1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR-1178 in human macrophages (HTP-1 and U937 cells) in a concentration- and time-dependent manner...
May 21, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29780528/synthetic-glycan-based-tlr4-agonists-targeting-caspase-4-11-for-the-development-of-adjuvants-and-immunotherapeutics
#17
Florian Adanitsch, Jianjin Shi, Feng Shao, Rudi Beyaert, Holger Heine, Alla Zamyatina
Gram-negative bacterial lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4) mediated pro-inflammatory signaling plays a key role in immunoprotection against infectious challenges and boosts adaptive immunity, whereas the activation of the cytosolic LPS receptor caspase-4/11 leads to cell death by pyroptosis and is deeply implicated in the development of sepsis. Despite tremendous advances in the understanding of the LPS-TLR4 interaction, predictably regulated TLR4 activation has not yet been achieved...
April 28, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780321/toll-like-receptor-2-signaling-and-current-approaches-for-therapeutic-modulation-in-synucleinopathies
#18
REVIEW
Ian F Caplan, Kathleen A Maguire-Zeiss
The innate immune response in the central nervous system (CNS) is implicated as both beneficial and detrimental to health. Integral to this process are microglia, the resident immune cells of the CNS. Microglia express a wide variety of pattern-recognition receptors, such as Toll-like receptors, that detect changes in the neural environment. The activation of microglia and the subsequent proinflammatory response has become increasingly relevant to synucleinopathies, including Parkinson's disease the second most prevalent neurodegenerative disease...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29780305/comparing-effects-of-transforming-growth-factor-%C3%AE-1-on-microglia-from-rat-and-mouse-transcriptional-profiles-and-potassium-channels
#19
Starlee Lively, Doris Lam, Raymond Wong, Lyanne C Schlichter
The cytokine, transforming growth factor β1 (TGFβ1), is up-regulated after central nervous system (CNS) injuries or diseases involving microglial activation, and it has been proposed as a therapeutic agent for treating neuroinflammation. Microglia can produce and respond to TGFβ1. While rats and mice are commonly used for studying neuroinflammation, very few reports directly compare them. Such studies are important for improving pre-clinical studies and furthering translational progress in developing therapeutic interventions...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29779787/a-thermodynamic-funnel-drives-bacterial-lipopolysaccharide-transfer-in-the-tlr4-pathway
#20
Roland G Huber, Nils A Berglund, Vasileios Kargas, Jan K Marzinek, Daniel A Holdbrook, Syma Khalid, Thomas J Piggot, Artur Schmidtchen, Peter J Bond
The Gram-negative bacterial outer membrane contains lipopolysaccharide, which potently stimulates the mammalian innate immune response. This involves a relay of specialized complexes culminating in transfer of lipopolysaccharide from CD14 to Toll-like receptor 4 (TLR4) and its co-receptor MD-2 on the cell surface, leading to activation of downstream inflammatory responses. In this study we develop computational models to trace the TLR4 cascade in near-atomic detail. We demonstrate through rigorous thermodynamic calculations that lipopolysaccharide molecules traversing the receptor cascade fall into a thermodynamic funnel...
April 25, 2018: Structure
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