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Toll Like Receptor(TLR)

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https://www.readbyqxmd.com/read/27919753/advax-a-delta-inulin-microparticle-potentiates-in-built-adjuvant-property-of-co-administered-vaccines
#1
Masayuki Hayashi, Taiki Aoshi, Yasunari Haseda, Kouji Kobiyama, Edward Wijaya, Noriyuki Nakatsu, Yoshinobu Igarashi, Daron M Standley, Hiroshi Yamada, Yoshikazu Honda-Okubo, Hiromitsu Hara, Takashi Saito, Toshiyuki Takai, Cevayir Coban, Nikolai Petrovsky, Ken J Ishii
Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen...
December 1, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27917620/normothermic-ex-vivo-lung-perfusion-in-brain-dead-donors-reduces-inflammatory-cytokines-and-toll-like-receptor-expression
#2
Shadi Shafaghi, Esmaeil Mortaz, Azizollah Abbasi Dezfuli, Hoda Godarzi, Kambiz Sheikhy, Zahra Ansari Aval, Behrooz Farzanegan, Habib Emami, Fatemeh Sadat Hosseini-Baharanchi, Katayoun Najafizadeh
Inflammatory responses and innate immunologic reactions play an important role in the respiratory system. Ex vivo lung perfusion (EVLP) is considered a novel method in the evaluation and reconditioning of donor lungs prior to transplantation. However, EVLP's effect on inflammatory and metabolic markers of human lung tissue is unknown.  This study investigated how the performance of EVLP on brain-dead (BD) donor lungs affects the production and release of inflammatory cytokines (IL-6, IL-8, and TNF-a), inflammatory cells and toll-like receptors (TLR) -2, 4...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27917375/recombinant-lipoprotein-rv1016c-derived-from-mycobacterium-tuberculosis-is-a-tlr-2-ligand-that-induces-macrophages-apoptosis-and-inhibits-mhc-ii-antigen-processing
#3
Haibo Su, Shenglin Zhu, Lin Zhu, Wei Huang, Honghai Wang, Zhi Zhang, Ying Xu
TLR2-dependent cellular signaling in Mycobacterium tuberculosis-infected macrophages causes apoptosis and inhibits class II major histocompatibility complex (MHC-II) molecules antigen processing, leading to evasion of surveillance. Mycobacterium tuberculosis (MTB) lipoproteins are an important class of Toll-like receptor (TLR) ligand, and identified as specific components that mediate these effects. In this study, we identified and characterized MTB lipoprotein Rv1016c (lpqT) as a cell wall associated-protein that was exposed on the cell surface and enhanced the survival of recombinants M...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27917262/toll-like-receptors-in-pathophysiology-of-liver-diseases
#4
REVIEW
Safak Kiziltas
Toll-like receptors (TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27916353/toll-like-receptor-responses-are-suppressed-in-trauma-icu-patients
#5
Travis L Holloway, Susannah E Nicholson, Meenakshi Rani, Andrew P Cap, Martin G Schwacha
BACKGROUND: Inflammation and activation of the innate immune system are often associated with traumatic injury and may involve alterations in toll-like receptor (TLR)-mediated responses. METHODS: A prospective observational study was designed and conducted. Twenty-one severely injured (ISS = 16-41) trauma intensive care unit (ICU) patients and six healthy volunteers that served as controls were enrolled. Anticoagulated whole blood was collected at 2-12 d after ICU admission and incubated in the presence of media alone (baseline), zymosan (TLR2 agonist) or lipopolysaccharide (LPS; TLR4 agonist) for 3 h...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27913143/innate-immune-stimulatory-activity-of-porphyromonas-gingivalis-fimbriae-is-eliminated-by-phase-separation-using-triton-x-114
#6
Kohji Nozoe, Terukazu Sanui, Masaaki Takeshita, Takao Fukuda, Akira Haraguchi, Yoshitomi Aida, Fusanori Nishimura
Fimbriae are virulence factors of Porphyromonas gingivalis (P. gingivalis). In this study, the action of fimbriae on neutrophil respiratory burst and cytokine production by mononuclear cells (MNC) were investigated. Native or denatured form of purified P. gingivalis fimbriae contained endotoxin at an equivalence of 1-3μglipopolysaccharides(LPS)/mg protein. The endotoxin could be reduced to the equivalent of 1ng-LPS/mg protein by phase separation using Triton X-114. Unfractionated fimbriae caused serum-dependent priming of neutrophils for enhanced respiratory burst, but both native and denatured forms of Triton X-114-fractionated fimbriae were not active at 100μg/mL...
November 30, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#7
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#8
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27909057/structure-of-the-tir-domain-of-bcap-which-links-phosphoinositide-metabolism-with-the-negative-regulation-of-the-tlr-signalosome
#9
Samer Halabi, Eiki Sekine, Brett Verstack, Nicholas J Gay, Martin C Moncrieffe
Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic TIR domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors, pro-inflammatory molecules and the activation of Phosphoinositide 3-kinases (PI3K) in a process that requires the multi-modular B-cell Adaptor for Phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain. Here, we present the structure of the N-terminal region of human BCAP and show that it possesses a canonical TIR-fold...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#10
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27902761/tlr-2-recognizes-propionibacterium-acnes-camp-factor-1-from-highly-inflammatory-strains
#11
Coralie Lheure, Philippe Alain Grange, Guillaume Ollagnier, Philippe Morand, Nathalie Désiré, Sophie Sayon, Stéphane Corvec, Jöel Raingeaud, Anne-Geneviève Marcelin, Vincent Calvez, Amir Khammari, Frédéric Batteux, Brigitte Dréno, Nicolas Dupin
BACKGROUND: Propionibacterium acnes (P. acnes) is an anaerobic, Gram-positive bacteria encountered in inflammatory acne lesions, particularly in the pilosebaceous follicle. P. acnes triggers a strong immune response involving keratinocytes, sebocytes and monocytes, the target cells during acne development. Lipoteicoic acid and peptidoglycan induce the inflammatory reaction, but no P. acnes surface protein interacting with Toll-like receptors has been identified. P. acnes surface proteins have been extracted by lithium stripping and shown to induce CXCL8 production by keratinocytes...
2016: PloS One
https://www.readbyqxmd.com/read/27898411/radioprotective-effects-of-heat-killed-mycobacterium-tuberculosis-in-cultured-cells-and-radiosensitive-tissues
#12
Yuanyuan Chen, Yang Xu, Jicong Du, Jiaming Guo, Xiao Lei, Jianguo Cui, Cong Liu, Ying Cheng, Bailong Li, Fu Gao, Jintao Ju, Jianming Cai, Yanyong Yang
BACKGROUND: Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR. METHODS: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27897392/toll-like-receptor-4-signalling-mediates-inflammation-in-skeletal-muscle-of-patients-with-chronic-kidney-disease
#13
Daniela Verzola, Alice Bonanni, Antonella Sofia, Fabrizio Montecucco, Elena D'Amato, Valeria Cademartori, Emanuele Luigi Parodi, Francesca Viazzi, Chiara Venturelli, Giuliano Brunori, Giacomo Garibotto
BACKGROUND: Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine...
October 18, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897273/a-novel-therapeutic-peptide-as-a-partial-agonist-of-rankl-in-ischemic-stroke
#14
Hitomi Kurinami, Munehisa Shimamura, Hironori Nakagami, Hideo Shimizu, Hiroshi Koriyama, Tomohiro Kawano, Kouji Wakayama, Hideki Mochizuki, Hiromi Rakugi, Ryuichi Morishita
The enhanced receptor activator of nuclear factor-κB (NFκB) ligand (RANKL) and its receptor (RANK) signal have been reported to attenuate ischemic brain injury through inhibition of Toll-like receptor (TLR) 4-mediated inflammation. However, augmentation of the RANKL/RANK signal also accelerates osteoporosis, which is a potential problem in clinical use of RANKL. Therefore, we developed novel peptides, microglial healing peptides (MHPs), which were based on the DE and/or EF loop of RANKL. Among them, MHP1 was the most effective inhibitor of TLR4-induced inflammations in microglia/macrophages...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895422/genetic-polymorphism-in-cd14-gene-a-co-receptor-of-tlr4-associated-with-non-alcoholic-fatty-liver-disease
#15
Shweta Kapil, Ajay Duseja, Bal Krishan Sharma, Bhupesh Singla, Anuradha Chakraborti, Ashim Das, Pallab Ray, Radha K Dhiman, Yogesh Chawla
AIM: To evaluate the pathogenic role of toll-like receptor (TLR) gene polymorphisms in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Two hundred and fifty subjects (NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2 (TLR2) gene (A753G), two polymorphisms in the TLR4 gene (TLR4 Asp299Gly and Thr399Ile allele), and two polymorphisms in the cluster of differentiation 14 (CD14) (C-159T and C-550T) gene, a co-receptor of TLR4...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27895398/dysregulation-of-innate-immunity-in-ulcerative-colitis-patients-who-fail-anti-tumor-necrosis-factor-therapy
#16
Angela C Baird, Dominic Mallon, Graham Radford-Smith, Julien Boyer, Thierry Piche, Susan L Prescott, Ian C Lawrance, Meri K Tulic
AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12)...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27895126/versican-deficiency-significantly-reduces-lung-inflammatory-response-induced-by-polyinosine-polycytidylic-acid-stimulation
#17
Inkyung Kang, Ingrid A Harten, Mary Y Chang, Kathleen R Braun, Alyssa Sheih, Mary P Nivison, Pamela Y Johnson, Gail Workman, Gernot Kaber, Stephen P Evanko, Christina K Chan, Mervyn J Merrilees, Steven F Ziegler, Michael G Kinsella, Charles W Frevert, Thomas N Wight
Viral infection is an exacerbating factor contributing to chronic airway diseases such as asthma via mechanisms which are still unclear. Polyinosine-polycytidylic acid (poly I:C), a toll-like receptor (TLR) 3 agonist used as a mimetic to study viral infection, has been shown to elicit inflammatory responses in lungs and to exacerbate pulmonary allergic reactions in animal models. Previously, we have shown that poly I:C stimulates lung fibroblasts to accumulate an extracellular matrix (ECM), enriched in hyaluronan (HA) and its binding partner versican, which promotes monocyte adhesion...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894923/therapeutic-implications-of-toll-like-receptors-in-peripheral-neuropathic-pain
#18
REVIEW
Krishan K Thakur, Jyoti Saini, Kanika Mahajan, Dhyanendra Singh, Dinkar P Jayswal, Srishti Mishra, Anupam Bishyaee, Gautam Sethi, Ajaikumar B Kunnumakkara
Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain...
November 25, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27891600/human-pdcs-display-sex-specific-differences-in-type-i-interferon-subtypes-and-interferon-%C3%AE-%C3%AE-receptor-expression
#19
Susanne Ziegler, Claudia Beisel, Kathrin Sutter, Morgane Griesbeck, Heike Hildebrandt, Sven Hagen, Ulf Dittmer, Marcus Altfeld
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR) 7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFNα-subtypes...
November 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27891130/molecular-mechanisms-that-underlie-the-dynamic-adaptation-of-innate-monocyte-memory-to-varying-stimulant-strength-of-tlr-ligands
#20
Ruoxi Yuan, Shuo Geng, Liwu Li
In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS...
2016: Frontiers in Immunology
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