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Toll-like Receptors

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https://www.readbyqxmd.com/read/28110170/tailoring-polymeric-hybrid-micelles-with-lymph-node-targeting-ability-to-improve-the-potency-of-cancer-vaccines
#1
Qin Zeng, Hanmei Li, Hao Jiang, Jiao Yu, Ying Wang, Huan Ke, Tao Gong, Zhirong Zhang, Xun Sun
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28110121/s100a12-friend-or-foe-in-pulmonary-tuberculosis
#2
Vahid Bagheri
In humans, S100A12 (also named Calgranulin C and EN-RAGE) is mainly expressed and secreted by neutrophil granulocytes. Extracellular S100A12 is involved in innate immune responses against microorganisms and parasites. S100A12 is a ligand for the receptor for advanced glycation end products (RAGE), which is a cell surface receptor on macrophages, endothelium, and lymphocytes. In a recent study, Realegeno et al. showed that S100A12 exerts antimicrobial activity against Mycobacterium leprae in infected human macrophages...
January 18, 2017: Cytokine
https://www.readbyqxmd.com/read/28110064/activation-of-dendritic-cells-by-low-molecular-weight-oyster-polysaccharides
#3
Ming Zhong, Cheng Zhong, Tingting Wang, Pei Hu, Guanghui Wang, Rujing Ren, Jing Zhang, Huijei Gao, Wen Cui, Wenjuan Duan, Jiantu Che
Dendritic cells play a primary role in antigen presentation to CD4(+) T cells, which initiate acquired immune responses. Therefore, determining positive modulators of dendritic cell activation to improve therapeutic approaches for cancer treatment might be useful. We here investigated the effects of low molecular weight oyster polysaccharides (LMW-OPS) on bone marrow-derived dendritic cells (BMDCs) obtained from mice. LMW-OPS increased the surface expression of major histocompatibility complex class II (MHC-II), CD40 and CD86 in BMDCs and induced the secretion of tumour necrosis factor (TNF)-α and interleukin (IL)-12, which were significantly decreased in the BMDCs derived from MyD88(-/-) mice but not from the lipopolysaccharide-resistant C3H/HeJ mice...
January 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28110063/curcumin-ameliorates-liver-damage-and-progression-of-nash-in-nash-hcc-mouse-model-possibly-by-modulating-hmgb1-nf-%C3%AE%C2%BAb-translocation
#4
Rejina Afrin, Somasundaram Arumugam, Azizur Rahman, Mir Imam Ibne Wahed, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Hiroyuki Yoneyama, Kazuyuki Ueno, Kenichi Watanabe
Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding...
January 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28109979/interferon-ifn-induced-protein-35-ifi35-negatively-regulates-ifn-%C3%AE-phosphorylated-stat1-rig-i-cxcl10-ccl5-axis-in-u373mg-astrocytoma-cells-treated-with-polyinosinic-polycytidylic-acid
#5
Kyogo Shirai, Taku Shimada, Hidemi Yoshida, Ryo Hayakari, Tomoh Matsumiya, Kunikazu Tanji, Manabu Murakami, Hiroshi Tanaka, Tadaatsu Imaizumi
Interferon (IFN)-stimulated genes (ISGs) exert multiple functions in immune system. IFN-induced protein 35 (IFI35) is a member of ISGs, and has been suggested to regulate innate immune reaction. However, the physiological functions and pathological roles of IFI35 in the central nervous system are not characterized well. In the present study, we found that the expression of IFI35 was induced by a Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid (poly IC) in U373MG human astrocytoma cells. Knockdown of IFI35 using RNA interference resulted in increased expression of IFN-β, phosphorylated STAT1 (P-STAT1), retinoic acid-inducible gene-I (RIG-I), CXCL10 and CCL5 induced by poly IC...
January 18, 2017: Brain Research
https://www.readbyqxmd.com/read/28109721/inflammasome-priming-in-sterile-inflammatory-disease
#6
REVIEW
Meghana N Patel, Richard G Carroll, Silvia Galván-Peña, Evanna L Mills, Robin Olden, Martha Triantafilou, Amaya I Wolf, Clare E Bryant, Kathy Triantafilou, Seth L Masters
The inflammasome is a cytoplasmic protein complex that processes interleukins (IL)-1β and IL-18, and drives a form of cell death known as pyroptosis. Oligomerization of this complex is actually the second step of activation, and a priming step must occur first. This involves transcriptional upregulation of pro-IL-1β, inflammasome sensor NLRP3, or the non-canonical inflammasome sensor caspase-11. An additional aspect of priming is the post-translational modification of particular inflammasome constituents...
January 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28109139/-imiquimod-combined-with-dendritic-cell-vaccine-decreases-treg-proportion-and-enhances-anti-tumor-responses-in-mice-bearing-melanoma
#7
Shurong Ren, Qiubo Wang, Yanli Zhang, Cuixiu Lu, Ping Li, Yumei Li
Objective To investigate the therapeutic effect of Toll-like receptor 7 (TLR7) agonist imiquimod combined with dendritic cell (DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57BL/6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant mouse interleukin-4 (rmIL-4)...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28108849/toll-like-receptor-4-affects-the-cerebral-biochemical-changes-induced-by-mptp-treatment
#8
Carmela Conte, Luca Roscini, Roccaldo Sardella, Giuseppina Mariucci, Stefania Scorzoni, Tommaso Beccari, Laura Corte
The etiology and pathogenesis of Parkinson's disease (PD) are still unclear. However, multiple lines of evidence suggest a critical role of the toll like receptor 4 (TLR4) in inflammatory response and neuronal death. Neuroinflammation may be associated with the misfolding and aggregation of proteins accompanied by a change in their secondary structure. Recent findings also suggest that biochemical perturbations in cerebral lipid content could contribute to the pathogenesis of central nervous system (CNS) disorders, including PD...
January 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28108469/blood-rna-biomarkers-in-prodromal-park4-and-rem-sleep-behavior-disorder-show-role-of-complexin-1-loss-for-risk-of-parkinson-s-disease
#9
Suna Lahut, Suzana Gispert, Özgür Ömür, Candan Depboylu, Kay Seidel, Jorge Antolio Domínguez-Bautista, Nadine Brehm, Hülya Tireli, Karl Hackmann, Caroline Pirkevi, Barbara Leube, Vincent Ries, Kerstin Reim, Nils Brose, Wilfred F den Dunnen, Madrid Johnson, Zsuzsanna Wolf, Marc Schindewolf, Wiebke Schrempf, Kathrin Reetz, Peter Young, David Vadasz, Achilleas S Frangakis, Evelin Schröck, Helmuth Steinmetz, Marina Jendrach, Udo Rüb, Ayşe Nazlı Başak, Wolfgang Oertel, Georg Auburger
Parkinson's disease (PD) is a frequent neurodegenerative process at old age. Accumulation and aggregation of the lipid-binding SNARE complex component alpha-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity are intensely investigated. In view of physiological SNCA roles in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation), to identify effects of SNCA gain-of-function as potential disease biomarkers...
January 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28108421/tlr4-knockout-attenuated-high-fat-diet-induced-cardiac-dysfunction-via-nf-%C3%AE%C2%BAb-jnk-dependent-activation-of-autophagy
#10
Nan Hu, Yingmei Zhang
Obesity is commonly associated with a low grade systematic inflammation, which may contribute to the onset and development of myocardial remodeling and contractile dysfunction. Toll-like receptor 4 (TLR4) plays an important role in innate immunity and inflammation although its role in high fat diet-induced obesity cardiac dysfunction remains elusive. This study was designed to examine the effect of TLR4 ablation on high fat diet intake-induced cardiac anomalies, if any, and underlying mechanism(s) involved...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108356/lipid-a-structural-modifications-in-extreme-conditions-and-identification-of-unique-modifying-enzymes-to-define-the-toll-like-receptor-4-structure-activity-relationship
#11
REVIEW
Alison J Scott, Benjamin L Oyler, David R Goodlett, Robert K Ernst
Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108340/rna-seq-transcriptome-analysis-of-the-olive-flounder-paralichthys-olivaceus-kidney-response-to-vaccination-with-heat-inactivated-viral-hemorrhagic-septicemia-virus
#12
Jee Youn Hwang, Mun Gyeoung Kwon, Sung-Hee Jung, Myoung Ae Park, Dong-Wook Kim, Wang Sik Cho, Jeong Woo Park, Maeng-Hyun Son
Viral hemorrhagic septicemia (VHS) is a highly contagious disease of cultured flounder caused by VHS virus (VHSV). To develop effective VHSV vaccines, it is essential to understand the molecular mechanisms underlying the host's protective response against VHSV. The purpose of this study is to clarify which genes are involved in the protective response of olive flounder after VHSV vaccination. We first injected olive flounder intraperitoneally with 10(7) TCID50 heat-inactivated VHSV vaccine and evaluated the vaccine efficacy at 20 °C...
January 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28108339/transcriptome-analysis-of-the-effect-of-polyunsaturated-fatty-acids-against-vibrio-vulnificus-infection-in-oreochromis-niloticus
#13
Chieh-Yu Pan, Yu-Hao Liu, Hong-Yi Gong, Jyh-Yih Chen
Vibrio vulnificus infection causes severe economic losses in Oreochromis niloticus aquaculture by inducing pro-inflammatory cytokines, that lead to inflammation and mortality. Omega-3 fatty acids, such as Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA), have been reported for their anti-inflammatory and antibacterial abilities in murine and zebrafish models. However, the anti-inflammatory and antibacterial functions of DHA and EPA in commercial aquaculture organisms such as Oreochromis niloticus remain unknown...
January 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28107512/nonstructural-5a-protein-of-hepatitis-c-virus-interferes-with-toll-like-receptor-signaling-and-suppresses-the-interferon-response-in-mouse-liver
#14
Takeya Tsutsumi, Kazuya Okushin, Kenichiro Enooku, Hidetaka Fujinaga, Kyoji Moriya, Hiroshi Yotsuyanagi, Hideki Aizaki, Tetsuro Suzuki, Yoshiharu Matsuura, Kazuhiko Koike
The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS) in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver...
2017: PloS One
https://www.readbyqxmd.com/read/28106541/cell-membrane-and-intracellular-expression-of-toll-like-receptor-9-tlr9-in-colorectal-cancer-and-breast-cancer-cell-lines
#15
Shadab Shahriari, Somayeh Rezaeifard, Hamid Reza Moghimi, Mohammad Reza Khorramizadeh, Zahra Faghih
BACKGROUND: Toll-like receptor 9 (TLR9) is a DNA receptor of innate immune system which plays a pivotal role in inflammatory response. Recent evidence reveals over-expression and functionality of TLR9 in a wide variety of cancer cells and its contribution to tumor cell proliferation and survival. OBJECTIVE: In this study, we assessed the aberrant cell surface expression of TLR9 in cancer using cell-lines model. METHODS: Three breast cancer cell-lines (MDA-MB-231, MCF7 and SKBR3) and five colorectal adenocarcinoma cell-lines (HT29, HT29/219, SW480, SW48 and SW1116) in addition to one primary foreskin isolated fibroblast cell were analyzed for cell surface and intracellular expression of TLR9 by flow cytometry method...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106157/tlr4-antagonist-fp7-inhibits-lps-induced-cytokine-production-and-glycolytic-reprogramming-in-dendritic-cells-and-protects-mice-from-lethal-influenza-infection
#16
Laure Perrin-Cocon, Anne Aublin-Gex, Stefania E Sestito, Kari Ann Shirey, Mira C Patel, Patrice André, Jorge C Blanco, Stefanie N Vogel, Francesco Peri, Vincent Lotteau
Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS)...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106112/a-conserved-tlr5-binding-and-activation-hot-spot-on-flagellin
#17
Wan Seok Song, Ye Ji Jeon, Byeol Namgung, Minsun Hong, Sung-Il Yoon
Flagellin is a bacterial protein that polymerizes into the flagellar filament and is essential for bacterial motility. When flagellated bacteria invade the host, flagellin is recognized by Toll-like receptor 5 (TLR5) as a pathogen invasion signal and eventually evokes the innate immune response. Here, we provide a conserved structural mechanism by which flagellins from Gram-negative γ-proteobacteria and Gram-positive Firmicutes bacteria bind and activate TLR5. The comparative structural analysis using our crystal structure of a complex between Bacillus subtilis flagellin (bsflagellin) and TLR5 at 2...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105084/picroside-ii-protects-myocardium-from-ischemia-reperfusion-induced-injury-through-inhibition-of-the-inflammatory-response
#18
Jian-Zhe Li, Mei-Qing Xie, Dan Mo, Xiao-Fang Zhao, Shu-Yi Yu, Li-Juan Liu, Cheng Wu, Yang Yang
The inflammatory response is important in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Picroside II, the primary active constituent of Picrorhizae, has been reported to protect the myocardium from I/R-induced injury, however, the exact mechanism underlying these protective effects remains unclear. The aim of the present study was to investigate the mechanism underlying the protective effects of picroside II on I/R-induced myocardial injury. Adult male Sprague-Dawley rats underwent 1 h left coronary artery occlusion followed by 3 h reperfusion...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28103949/activation-of-human-b-cells-negatively-regulates-tgf-%C3%AE-1-production
#19
Nicolas Molnarfi, Kristbjörg Bjarnadóttir, Mahdia Benkhoucha, Catherine Juillard, Patrice H Lalive
BACKGROUND: Accumulating evidence indicate that B cells can exhibit pro- or anti-inflammatory activities. Similar to interleukin (IL)-10-competent B cells, we recently showed that transforming growth factor (TGF)-β1-producing regulatory B cells limit the induction of autoimmune neuroinflammation in mice, making them potentially important in maintaining peripheral immune tolerance in central nervous system inflammatory demyelinating disorders such as multiple sclerosis. METHODS: In this study, we compared B cell production of TGF-β1 and IL-10, the two most studied regulatory cytokines, and the pro-inflammatory B cell-derived IL-6 and tumor necrosis factor cytokines under basal conditions and following polyclonal stimulation with dual B cell receptor (BCR) cross-linking and Toll-like receptor (TLR)9 engagement...
January 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#20
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
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