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Tlr4, tlr2, toll like receptor,

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https://www.readbyqxmd.com/read/28209121/evolution-of-toll-like-receptors-in-the-context-of-terrestrial-ungulates-and-cetaceans-diversification
#1
Edson Ishengoma, Morris Agaba
BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi together afforded the opportunity to examine the evolution of selected TLRs in broad range of terrestrial ungulates and cetaceans during their complex habitat diversification. Through direct sequence comparisons and standard evolutionary approaches, the extent of nucleotide and protein sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5, TLR7, TLR9 and TLR10) between giraffe and closely related species was determined...
February 16, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28205610/cr-laao-an-l-amino-acid-oxidase-from-calloselasma-rhodostoma-venom-as-a-potential-tool-for-developing-novel-immunotherapeutic-strategies-against-cancer
#2
Tássia R Costa, Danilo L Menaldo, Karina F Zoccal, Sandra M Burin, Alexandre F Aissa, Fabíola A de Castro, Lúcia H Faccioli, Lusânia M Greggi Antunes, Suely V Sampaio
L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced in vivo and in vitro by CR-LAAO, an L-amino acid oxidase isolated from Calloselasma rhodostoma venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses in vivo, with recruitment of neutrophils and release of IL-6, IL-1β, LTB4 and PGE2. In vitro, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191612/high-toll-like-receptor-tlr-9-expression-is-associated-with-better-prognosis-in-surgically-treated-pancreatic-cancer-patients
#3
Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Petri Lehenkari, Juha Saarnio, Tuomo J Karttunen
Pancreatic cancer remains one of the deadliest malignancies in the world. Inflammatory response and tumor environment are thought to play a major role in its pathogenesis. Knowledge on TLR expression and impact on patient survival in pancreatic cancer is limited. The study's aim was to clarify the role of different TLRs in pancreatic cancer. TLR2, TLR4, and TLR9 expression was investigated in 65 surgically resected pancreatic ductal adenocarcinoma specimens by immunohistochemistry. The association between TLR expression, clinical parameters, and local inflammatory response to the tumor was assessed using chi-square test...
February 12, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28184217/chlamydial-lipoproteins-stimulate-toll-like-receptors-1-2-mediated-inflammatory-responses-through-myd88-dependent-pathway
#4
Yong Wang, Qiong Liu, Ding Chen, Jie Guan, Linghui Ma, Guangming Zhong, Hengping Shu, Xiang Wu
Chlamydiae are very important pathogens which could cause several types of diseases in human, but little is known about its pathogenic mechanism. In order to elucidate host inflammatory response and the signal pathway induced by Chlamydial lipoproteins, the predicted lipoproteins of Chlamydia trachomatis were tested for their ability to induce the release of proinflammatory cytokines by mouse macrophages or human TLR (Toll-Like Receptor) expressing cell lines. The results showed that recombinant proteins of C...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28171866/selective-biological-responses-of-phagocytes-and-lungs-to-purified-histones
#5
Fatemeh Fattahi, Jamison J Grailer, Hope Lu, Rachel S Dick, Michella Parlett, Firas S Zetoune, Gabriel Nuñez, Peter A Ward
Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B...
February 8, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28166799/toll-like-receptor-3-activation-selectively-reverses-hiv-latency-in-microglial-cells
#6
David Alvarez-Carbonell, Yoelvis Garcia-Mesa, Stephanie Milne, Biswajit Das, Curtis Dobrowolski, Roxana Rojas, Jonathan Karn
BACKGROUND: Multiple toll-like receptors (TLRs) are expressed in cells of the monocytic lineage, including microglia, which constitute the major reservoir for human immunodeficiency virus (HIV) infection in the brain. We hypothesized that TLR receptor mediated responses to inflammatory conditions by microglial cells in the central nervous system (CNS) are able to induce latent HIV proviruses, and contribute to the etiology of HIV-associated neurocognitive disorders. RESULTS: Newly developed human microglial cell lines (hµglia), obtained by immortalizing human primary microglia with simian virus-40 (SV40) large T antigen and the human telomerase reverse transcriptase, were used to generate latently infected cells using a single-round HIV virus carrying a green fluorescence protein reporter (hµglia/HIV, clones HC01 and HC69)...
February 6, 2017: Retrovirology
https://www.readbyqxmd.com/read/28166601/mechanisms-of-cellular-activation-in-the-antiphospholipid-syndrome
#7
Nadine Müller-Calleja, Karl J Lackner
It is long known that antiphospholipid antibodies (aPL) induce proinflammatory and procoagulant cellular responses. The underlying signal transduction has been a major focus of research and is the topic of this review. An amazingly heterogeneous panel of signaling pathways has been described and it turns out that at least some of this heterogeneity can be explained by effects of distinct aPL species. On the one hand, there are antibodies against β2-glycoprotein I (β2GPI) which appear to exert their cellular effects only as a complex of β2GPI/anti-β2GPI...
February 6, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28161794/preparation-of-the-extracellular-domain-of-recombinant-human-toll-like-receptor-6
#8
Takuya Miyakawa, Ayane Kumazawa, Yoko Fuke, Toshiro Noshita, Yumiko Miyauchi, Masahiro Okada, Masaru Tanokura
Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker...
February 4, 2017: Protein Journal
https://www.readbyqxmd.com/read/28160299/sedative-and-motor-incoordination-effects-of-ethanol-in-mice-lacking-cd14-tlr2-tlr4-or-myd88
#9
Yuri A Blednov, Mendy Black, Jillian M Benavidez, Adriana Da Costa, Jody Mayfield, R Adron Harris
BACKGROUND: In our companion article, we examined the role of MyD88-dependent signaling in ethanol (EtOH) consumption in mice lacking key components of this inflammatory pathway and observed differential effects on drinking. Here, we studied the role of these same signaling components in the acute sedative, intoxicating, and physiological effects of EtOH. Toll-like receptor 4 (TLR4) has been reported to strongly reduce the duration of EtOH-induced sedation, although most studies do not support its direct involvement in EtOH consumption...
February 3, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28148965/rapid-detection-of-functional-gene-polymorphisms-of-tlrs-and-il-17-using-high-resolution-melting-analysis
#10
Johanna Teräsjärvi, Antti Hakanen, Matti Korppi, Kirsi Nuolivirta, Kirsi Gröndahl-Yli-Hannuksela, Jussi Mertsola, Ville Peltola, Qiushui He
Genetic variations in toll-like receptors (TLRs) and IL-17A have been widely connected to different diseases. Associations between susceptibility and resistance to different infections and single nucleotide polymorphisms (SNPs) in TLR1 to TLR4 and IL17A have been found. In this study, we aimed to develop a rapid and high throughput method to detect functional SNPs of above mentioned proteins. The following most studied and clinically important SNPs: TLR1 (rs5743618), TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790) and IL17 (rs2275913) were tested...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28146272/ethanol-consumption-in-mice-lacking-cd14-tlr2-tlr4-or-myd88
#11
Yuri A Blednov, Mendy Black, Julia Chernis, Adriana Da Costa, Jody Mayfield, R Adron Harris
BACKGROUND: Molecular and behavioral studies support a role for innate immune proinflammatory pathways in mediating the effects of alcohol. Increased levels of Toll-like receptors (TLRs) have been observed in animal models of alcohol consumption and in human alcoholics, and many of these TLRs signal via the MyD88-dependent pathway. We hypothesized that this pathway is involved in alcohol drinking and examined some of its key signaling components. METHODS: Different ethanol (EtOH)-drinking paradigms were studied in male and female control C57BL/6J mice versus mice lacking CD14, TLR2, TLR4 (C57BL/10ScN), or MyD88...
February 1, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28126350/peptostreptococcus-anaerobius-induces-intracellular-cholesterol-biosynthesis-in-colon-cells-to-induce-proliferation-and-causes-dysplasia-in-mice
#12
Ho Tsoi, Eagle Sh Chu, Xiang Zhang, Jianqiu Sheng, Daniel Nakatsu, Siew C Ng, Anthony Wh Chan, Francis Kl Chan, Joseph Jy Sung, Jun Yu
BACKGROUND & AIMS: Stool samples from patients with colorectal cancer (CRC) have a higher abundance of Peptostreptococcus anaerobius than stool from individuals without CRC, based on metagenome sequencing. We investigated whether P anaerobius contributes to colon tumor formation in mice and its possible mechanisms of carcinogenesis. METHODS: We performed quantitative PCR analyses to measure P anaerobius in 112 stool samples and 255 colon biopsies from patients with CRC or advanced adenoma and from healthy individuals (controls) undergoing colonoscopy examination at hospitals in Hong Kong and Beijing...
January 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28121465/topical-application-of-the-anti-microbial-chemical-triclosan-induces-immunomodulatory-responses-through-the-s100a8-a9-tlr4-pathway
#13
Nikki B Marshall, Ewa Lukomska, Ajay P Nayak, Carrie M Long, Justin M Hettick, Stacey E Anderson
The anti-microbial compound triclosan is incorporated into numerous consumer products and is detectable in the urine of 75% of the general United States population. Recent epidemiological studies report positive associations with urinary triclosan levels and allergic disease. Although not sensitizing, earlier studies previously found that repeated topical application of triclosan augments the allergic response to ovalbumin (OVA) though a thymic stromal lymphopoietin (TSLP) pathway in mice. In the present study, early immunological effects following triclosan exposure were further evaluated following topical application in a murine model...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28120492/the-role-of-toll-like-and-protease-activated-receptors-and-associated-intracellular-signaling-in-porphyromonas-gingivalis-infected-gingival-fibroblasts
#14
Eleonor Palm, Isak Demirel, Torbjörn Bengtsson, Hazem Khalaf
Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P...
February 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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
#15
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/28093922/toll-like-receptors-and-their-soluble-forms-differ-in-the-knee-and-thumb-basal-osteoarthritic-joints
#16
Goncalo Barreto, Jerker Sandelin, Abdelhakim Salem, Dan C Nordström, Eero Waris
Background and purpose - Although the pathogenesis of osteoarthritis (OA) is not well understood, chondrocyte-mediated inflammatory responses (triggered by the activation of innate immune receptors by damage-associated molecules) are thought to be involved. We examined the relationship between Toll-like receptors (TLRs) and OA in cartilage from 2 joints differing in size and mechanical loading: the first carpometacarpal (CMC-I) and the knee. Patients and methods - Samples of human cartilage obtained from OA CMC-I and knee joints were immunostained for TLRs (1-9) and analyzed using histomorphometry and principal component analysis (PCA)...
January 17, 2017: Acta Orthopaedica
https://www.readbyqxmd.com/read/28089363/pertussis-toxin-targets-the-innate-immunity-through-dap12-fcr%C3%AE-and-myd88-adaptor-proteins
#17
Vongsavanh Phongsisay, Ei'ichi Iizasa, Hiromitsu Hara, Hiroki Yoshida
Activation of the innate immunity by adjuvants, such as pertussis toxin (PTX), in the presence of autoreactive lymphocytes and antigen mimicry is sufficient to trigger autoimmunity. Toll-like, C-type lectin, and immunglobulin-like receptors play an important role in the innate immunity by sensing a variety of microbial products through several adaptor proteins, including MyD88, DAP12, and FcRγ. This study investigated the interaction between PTX and innate immune components. The direct interactions between coated PTX and receptor-fusion proteins were examined using ELISA-based binding assays...
December 30, 2016: Immunobiology
https://www.readbyqxmd.com/read/28089357/localization-of-toll-like-receptor-tlr-2-and-tlr4-mrna-in-the-colorectal-mucosa-of-miniature-dachshunds-with-inflammatory-colorectal-polyps
#18
N Yokoyama, H Ohta, J Yamazaki, Y Kagawa, O Ichii, N Khoirun, T Morita, T Osuga, S Y Lim, N Sasaki, K Morishita, K Nakamura, M Takiguchi
Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay...
January 12, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#19
Erika Della Mina, Alessandro Borghesi, Hao Zhou, Salim Bougarn, Sabri Boughorbel, Laura Israel, Ilaria Meloni, Maya Chrabieh, Yun Ling, Yuval Itan, Alessandra Renieri, Iolanda Mazzucchelli, Sabrina Basso, Piero Pavone, Raffaele Falsaperla, Roberto Ciccone, Rosa Maria Cerbo, Mauro Stronati, Capucine Picard, Orsetta Zuffardi, Laurent Abel, Damien Chaussabel, Nico Marr, Xiaoxia Li, Jean-Laurent Casanova, Anne Puel
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28060920/the-tir-homologue-lies-near-resistance-genes-in-staphylococcus-aureus-coupling-modulation-of-virulence-and-antimicrobial-susceptibility
#20
Sabine Patot, Paul Rc Imbert, Jessica Baude, Patricia Martins Simões, Jean-Baptiste Campergue, Arthur Louche, Reindert Nijland, Michèle Bès, Anne Tristan, Frédéric Laurent, Adrien Fischer, Jacques Schrenzel, François Vandenesch, Suzana P Salcedo, Patrice François, Gérard Lina
Toll/interleukin-1 receptor (TIR) domains in Toll-like receptors are essential for initiating and propagating the eukaryotic innate immune signaling cascade. Here, we investigate TirS, a Staphylococcus aureus TIR mimic that is part of a novel bacterial invasion mechanism. Its ectopic expression in eukaryotic cells inhibited TLR signaling, downregulating the NF-kB pathway through inhibition of TLR2, TLR4, TLR5, and TLR9. Skin lesions induced by the S. aureus knockout tirS mutant increased in a mouse model compared with wild-type and restored strains even though the tirS-mutant and wild-type strains did not differ in bacterial load...
January 2017: PLoS Pathogens
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