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Toll Like Receptor(TLR)

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https://www.readbyqxmd.com/read/28734965/enhanced-immunostimulatory-activity-of-in-silico-discovered-agonists-of-toll-like-receptor-2-tlr2
#1
M S Murgueitio, S Ebner, P Hörtnagl, C Rakers, R Bruckner, P Henneke, G Wolber, S Santos-Sierra
BACKGROUND: Emergent therapies in anticancer vaccination use Toll-like receptors (TLRs) agonists as dendritic cell (DC) vaccine adjuvants. DCs from the patient are isolated, stimulated with TLR agonists and tumor antigens ex vivo and then infused back into the patient. Although some TLR ligands have been tested in clinical trials, novel TLR agonists with improved immunomodulatory properties are essential to optimize treatment success. We report on the discovery of small-molecule TLR2 agonists, with favorable properties as synthetic adjuvants...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734835/migration-ability-and-toll-like-receptor-expression-of-human-mesenchymal-stem-cells-improves-significantly-after-three-dimensional-culture
#2
Panpan Zhou, Zilin Liu, Xue Li, Bing Zhang, Xiaoyuan Wang, Jing Lan, Qing Shi, Dong Li, Xiuli Ju
While the conventional two-dimensional (2D) culture protocol is well accepted for the culture of mesenchymal stem cells (MSCs), this method fails to recapitulate the in vivo native three-dimensional (3D) cellular microenvironment, and may result in phenotypic changes, and homing and migration capacity impairments. MSC preparation in 3D culture systems has been considered an attractive preparatory and delivery method recently. We seeded human umbilical cord-derived MSCs (hUCMSCs) in a 3D culture system with porcine acellular dermal matrix (PADM), and investigated the phenotypic changes, the expression changes of some important receptors, including Toll-like receptors (TLRs) and C-X-C chemokine receptor type 4 (CXCR4) when hUCMSCs were transferred from 2D to 3D systems, as well as the alterations in in vivo homing and migration potential...
July 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28730622/susceptibility-to-hiv-1-infection-is-influenced-by-toll-like-receptor-2-196-to-174-polymorphism-in-north-indian-population
#3
Sanjukta Vidyant, Animesh Chatterjee, Vikas Agarwal, Tapan N Dhole
INTRODUCTION: Toll like receptors (TLRs) are pattern recognition receptors, recognize molecular patterns of pathogens and play an important role in innate immunity. Recent studies have identified that single nucleotide polymorphism (SNPs) in TLR gene impairs the response to TLR ligands in some individuals and is associated with susceptibility to various infectious diseases. AIM: The aim of the present study is to investigate the role of four SNPs in the TLR2 gene, -196 to -174 Ins/Del, 2258 G/A (Arg753Gln), 2029 C/T (Arg677Trp) and 1892 C/A (Pro631His) with susceptibility and progression to HIV-1 in North Indian individuals...
July 20, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28730487/a-methodology-for-comprehensive-analysis-of-toll-like-receptor-signaling-in-macrophages
#4
Marijke Koppenol-Raab, Aleksandra Nita-Lazar
A combination of high-throughput, multiplexed, quantitative methods with computational modeling and statistical approaches is required to obtain system-level understanding of biological function. Mass spectrometry (MS)-based proteomics has emerged as a preferred tool for the analysis of changes in protein abundance and their post-translational modification (PTM) levels at a global scale, comparable with genomic experiments and generating data suitable for use in mathematical modeling of signaling pathways. Here we describe a set of parallel bottom-up proteomic approaches to detect and quantify the global protein changes in total intracellular proteins, their phosphorylation, and the proteins released by active and passive secretion or shedding mechanisms (referred to as the secretome as reviewed in Makridakis and Vlahou, J Proteome 73:2291-2305, 2010) in response to the stimulation of Toll-like receptors (TLRs) with specific ligands in cultured macrophages...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730145/prokaryotic-rna-associated-to-bacterial-viability-induces-polymorphonuclear-neutrophil-activation
#5
Nahuel Rodriguez-Rodrigues, Luis A Castillo, Verónica I Landoni, Daiana Martire-Greco, M Ayelén Milillo, Paula Barrionuevo, Gabriela C Fernández
Polymorphonuclear neutrophils (PMN) are the first cellular line of antibacterial host defense. They sense pathogens through recognition of pathogen-associated molecular patterns (PAMPs) by innate pattern recognition receptors, such as Toll-like receptors (TLR). The aim of this study was to investigate whether PMN sense bacterial viability and explore which viability factor could be involved in this phenomenon. For this purpose, different functions were evaluated in isolated human PMN using live Escherichia coli (Ec) and heat-killed Ec (HK-Ec)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28726298/faah-but-not-magl-inhibition-modulates-acute-tlr3-induced-neuroimmune-signaling-in-the-rat-independent-of-sex
#6
Lisa E Flannery, Rebecca J Henry, Daniel M Kerr, David P Finn, Michelle Roche
Toll-like receptor (TLR)3 is a key component of the innate immune response to viral infection. The present study firstly examined whether sex differences exist in TLR3-induced inflammatory, endocrine, and sickness responses. The data revealed that TLR3-induced expression of interferon- or NFkB-inducible genes (IFN-α/β, IP-10, or TNF-α), either peripherally (spleen) or centrally (hypothalamus), did not differ between male and female rats, with the exception of TLR3-induced IFN-α expression in the spleen of female, but not male, rats 8 hr post TLR3 activation...
July 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28725012/phycocyanin-attenuates-pulmonary-fibrosis-via-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#7
Chengcheng Li, Yan Yu, Wenjun Li, Bo Liu, Xudong Jiao, Xinyu Song, Changjun Lv, Song Qin
Our aim was to investigate the effects of phycocyanin (PC) on bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, C57 BL/6 wild-type (WT) mice and toll-like receptor (TLR) 2 deficient mice were treated with PC for 28 days following BLM exposure. Serum and lung tissues were collected on days 3, 7 and 28. Data shows PC significantly decreased the levels of hydroxyproline (HYP), vimentin, surfactant-associated protein C (SP-C), fibroblast specific protein-1 (S100A4) and α-smooth muscle actin (α-SMA) but dramatically increased E-cadherin and podoplanin (PDPN) expression on day 28...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#8
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#9
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723271/development-of-three-orthogonal-assays-suitable-for-the-identification-and-qualification-of-pikfyve-inhibitors
#10
Kylie Fogarty, Mohammed Kashem, Andras Bauer, Alexandra Bernardino, Debra Brennan, Brian Cook, Neil Farrow, Teresa Molinaro, Richard Nelson
FYVE-type zinc finger-containing phosphoinositide kinase (PIKfyve) catalyzes the formation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) from phosphatidylinositol 3-phosphate (PI(3)P). PIKfyve has been implicated in multiple cellular processes, and its role in the regulation of toll-like receptor (TLR) pathways and the production of proinflammatory cytokines has sparked interest in developing small-molecule PIKfyve inhibitors as potential therapeutics to treat autoimmune and inflammatory diseases. We developed three orthogonal assays to identify and qualify small-molecule inhibitors of PIKfyve: (1) a purified component microfluidic enzyme assay that measures the conversion of fluorescently labeled PI(3)P to PI(3,5)P2 by purified recombinant full-length human 6His-PIKfyve (rPIKfyve); (2) an intracellular protein stabilization assay using the kinase domain of PIKfyve expressed in HEK293 cells; and (3) a cell-based functional assay that measures the production of interleukin (IL)-12p70 in human peripheral blood mononuclear cells stimulated with TLR agonists lipopolysaccharide and R848...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28718060/innate-immune-responses-and-osteoarthritis
#11
REVIEW
Evangelia Kalaitzoglou, Timothy M Griffin, Mary Beth Humphrey
PURPOSE OF THE REVIEW: Osteoarthritis (OA) is a chronic, painful joint disease that affects approximately 40% of adults over 70 year. Age is the strongest predictor of OA, while obesity is considered the primary preventable risk factor for OA. Both conditions are associated with abnormal innate immune inflammatory responses that contribute to OA progression and are the focus of this review. RECENT FINDINGS: Recent studies have identified risk factors for OA progression including increased innate immune responses secondary to aging-associated myeloid skewing, obesity-related myeloid activation, and synovial tissue hyperplasia with activated macrophage infiltration...
August 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28717003/surface-toll-like-receptor-3-expression-in-metastatic-intestinal-epithelial-cells-induces-inflammatory-cytokine-production-and-promotes-invasiveness
#12
Marit Bugge, Bjarte Bergstrom, Oda Kamilla Eide, Helene Solli, Ingrid F Kjønstad, Jørgen Stenvik, Terje Espevik, Nadra J Nilsen
Toll-like receptors (TLR)s are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (Poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNβ production. Here, we report that unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3, and that TLR3 promotes invasiveness of these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716464/modulating-effects-of-omega-3-fatty-acids-and-pioglitazone-combination-on-insulin-resistance-through-toll-like-receptor-4-in-type-2-diabetes-mellitus
#13
Salma M Eraky, Noha Abdel-Rahman, Laila A Eissa
Toll-like receptor 4 (TLR-4) plays important roles in innate immunity. Changes in the reduction-oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance. An action thought to be mediated by TLRs. Omega-3 fatty acids and Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) agonists as pioglitazone are used for decreasing inflammation. The aim of this study is to investigate the anti-diabetic effects of combining omega -3 fatty acid with pioglitazone on type 2 diabetes, and the modifying effects on TLR-4...
June 17, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28715808/retinoic-acid-facilitates-toll-like-receptor-4-expression-to-improve-intestinal-barrier-function-through-retinoic-acid-receptor-beta
#14
Yingying Li, Yuan Gao, Ting Cui, Ting Yang, Lan Liu, Tingyu Li, Jie Chen
BACKGROUND/AIMS: Vitamin A (VA) protects the intestinal epithelial barrier by improving cell migration and proliferation. Our previous studies demonstrated that VA deficiency (VAD) during pregnancy suppresses the systemic and mucosal immune responses in the intestines of offspring and that VA supplementation (VAS) during early life can increase immune cell counts. However, little is known about the mechanisms by which VA regulates intestinal epithelial barrier function. METHODS: Caco-2 cells were treated with all-trans retinoic acid (ATRA) for 24 hours to determine the optimum ATRA concentration to which the cells in question respond...
July 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28715767/non-human-primates-as-a-model-for-understanding-the-mechanism-of-action-of-toll-like-receptor-based-vaccine-adjuvants
#15
REVIEW
Elizabeth A Thompson, Karin Loré
While transgenic mouse models are powerful for understanding how the immune system is manipulated by vaccines, they cannot fully recapitulate the characteristics of the innate immune responses leading to adaptive immunity after vaccination in humans. Outbred non-human primates are far more representative models of human vaccine responses as there is high degree of similarities in immune cell subset distributions, receptor expression (including toll-like receptors; TLRs), and immune cell functions, in addition to modeling doses and injection sites more accurately...
July 14, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28715645/characteristics-of-regulatory-b-cells-in-patients-with-chronic-hepatitis-b-virus-infection-in-different-immune-phases
#16
Guiyang Wang, Yong Liu, Rui Huang, Bei Jia, Ran Su, Zhenhua Sun, Chen Tian, Yali Xiong, Juan Xia, Xiaomin Yan, Zhaoping Zhang, Chao Wu
Regulatory B cells (Bregs) are reported to play an important role in the immune responses to chronic hepatitis B virus (HBV) via Toll-like-receptors (TLRs) signaling. We aimed to investigate the characteristics of Bregs and the expressions of TLRs in Bregs in the peripheral blood of different immune phases of patients with chronic HBV infection. In this study, we determined the frequencies of Bregs and TLR9, TLR2, and TLR4 in peripheral blood using flow cytometry and determined the levels of IL-10 in serum with the Human Magnetic Cytokine/Chemokine Bead Panel...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28715461/tlr1-10-nf-%C3%AE%C2%BAb-and-p53-expression-is-increased-in-oral-lichenoid-disease
#17
Peter Rusanen, Emilia Marttila, Johanna Uittamo, Jaana Hagström, Tuula Salo, Riina Rautemaa-Richardson
Toll-like receptors (TLRs) and nuclear factor-κB (NF-κB) in keratinocytes play an important role in dermatological autoimmune diseases. Tumour suppressor protein p53 regulates TLR expression. The aim of this study was to compare the expression of TLR1-TLR10, p53 and NF-κB in patients with oral lichenoid disease (OLD) with healthy mucosa. Oral mucosal biopsies from 24 patients with OLD and 26 healthy controls (HC) were analysed for the expression of TLR1-TLR10, NF-κB and p53 by immunohistochemistry. The expression of all TLRs was increased in OLD epithelia compared to HC samples and the difference was significant in TLR1, TLR3, TLR4, TLR5, TLR6 and TLR7...
2017: PloS One
https://www.readbyqxmd.com/read/28714872/immunomodulatory-activity-of-octenyl-succinic-anhydride-modified-porang-amorphophallus-oncophyllus-glucomannan-on-mouse-macrophage-like-j774-1-cells-and-mouse-primary-peritoneal-macrophages
#18
Sellen Gurusmatika, Kosuke Nishi, Eni Harmayani, Yudi Pranoto, Takuya Sugahara
Porang is a local plant of Indonesia, which has a high content of glucomannan. In this study, porang glucomannan (PG) was esterified with octenyl succinic anhydride (OSA) to enhance emulsion properties to be widely used in food industry. OSA-modified PG (OSA-PG) enhanced the phagocytosis activity of macrophage-like J774.1 cells and mouse peritoneal macrophages. In addition, OSA-PG increased the production of IL-6 and TNF-α by enhancing their gene expression. Immunoblot analysis displayed that OSA-PG tended to activate both nuclear factor-κB and mitogen-activated protein kinase cascades...
July 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28714001/lps-enhances-tlr4-expression-and-ifn%C3%A2-%C3%AE-production-via-the-tlr4-irak-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway-in-rat-pulmonary-arterial-smooth-muscle-cells
#19
Pengyan Wang, Xuhui Han, Biwen Mo, Guojin Huang, Changming Wang
The aim of the present study was to investigate the role of the Toll‑like receptor (TLR)4 signaling pathway in cellular response to lipopolysaccharide (LPS) in rat pulmonary artery smooth muscle cells (PASMCs). Chronic obstructive pulmonary disease (COPD) rats were established with passive inhaling cigarette smoke plus injection of LPS. The TLR4 protein in lung tissues was determined with immunohistochemical staining and protein levels of the components of the TLR4 pathway in PASMCs were analyzed with western blotting...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713897/expression-of-irak%C3%A2-3-is-associated-with-colitis%C3%A2-associated-tumorigenesis-in-mice
#20
Dingting Xu, Hanyun Zhang, Xiaoying Wang, Yan Chen
Interleukin‑1 receptor‑associated kinase‑3 (IRAK‑3) is a negative regulator in Toll‑like receptor (TLR) pathways. The present study investigated the importance of IRAK‑3 in a mouse model of chemically‑induced colitis‑associated tumorigenesis. The colitis‑associated tumorigenesis was induced in ICR mice by the administration of 1,2‑dimethyl hydrazine (DMH) and dextran sodium sulfate (DSS), termed the DMH + DSS group. In the DSS group, mice were administered with DSS; in the DMH group, mice were injected with DMH; in the control group, mice were injected with physiological saline...
July 12, 2017: Molecular Medicine Reports
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