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Toll Like Receptor(TLR)

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https://www.readbyqxmd.com/read/28431112/long-term-survival-of-the-mouse-es-cell-derived-mast-cell-medmc-brc6-in-mast-cell-deficient-kitw-sh-w-sh-mice
#1
Shohei Shibagaki, Satoko Tahara-Hanaoka, Takashi Hiroyama, Yukio Nakamura, Akira Shibuya
Mast cells (MCs) play pivotal roles in allergic reactions and the host defense against microbial infection through the immunoglobulin E (IgE)-dependent and IgE-independent signaling pathways. MC lines that can be analyzed both in vitro and in vivo would be useful for the study of MC-dependent immune responses. Here we investigated the functional characteristics of a mouse ES cell-derived mast cell-like cell line, MEDMC-BRC6. The cell line expressed FcεRI and c-Kit and showed degranulation and production of inflammatory cytokines and chemokine, including TNF-α, IL-6 and MCP-1, upon crosslinking FcεRI with IgE...
April 18, 2017: International Immunology
https://www.readbyqxmd.com/read/28429728/a-formulated-tlr7-8-agonist-is-a-flexible-highly-potent-and-effective-adjuvant-for-pandemic-influenza-vaccines
#2
Neal Van Hoeven, Christopher B Fox, Brian Granger, Tara Evers, Sharvari W Joshi, Ghislain I Nana, Sarah C Evans, Susan Lin, Hong Liang, Li Liang, Rie Nakajima, Philip L Felgner, Richard A Bowen, Nicole Marlenee, Airn Hartwig, Susan L Baldwin, Rhea N Coler, Mark Tomai, James Elvecrog, Steven G Reed, Darrick Carter
Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428828/bioinformatics-analysis-of-key-genes-and-latent-pathway-interactions-based-on-the-anaplastic-thyroid-carcinoma-gene-expression-profile
#3
Yun Huang, Yiming Tao, Xinying Li, Shi Chang, Bo Jiang, Feng Li, Zhi-Ming Wang
Anaplastic thyroid carcinoma (ATC) is an aggressive malignant disease in older adults with a high mortality rate. The present study aimed to examine several key genes and pathways, which are associated with ATC. The GSE33630 gene expression profile was downloaded from the Gene Expression Omnibus database, which included 11 ATC and 45 normal thyroid samples. The differentially expressed genes (DEGs) in ATC were identified using the Limma package in R. The Gene Ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways of the selected DEGs were enriched using the Database for Annotation, Visualization and Integrated Discovery...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#4
Thomas Ondet, Béatrice Muscatelli-Groux, Cédric Coulouarn, Sacha Robert, Thomas Gicquel, Aude Bodin, Vincent Lagente, Jean-Alexis Grimaud
Toll like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the three-dimensional structure of pathogen associated molecules and are thus useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides (LPS) and monosodium urate (MSU) crystals in the activation of the TLR and Nod Like Receptors (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NLRP3 and TLR4, both of which are components of inflammasome complexes involved in the activation of IL-1β, were not expressed in keratinocytes...
April 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28424405/the-bruton-s-tyrosine-kinase-inhibitor-ibrutinib-exerts-immunomodulatory-effects-through-regulation-of-tumor-infiltrating-macrophages
#5
Lingyan Ping, Ning Ding, Yunfei Shi, Lixia Feng, Jiao Li, Yalu Liu, Yufu Lin, Cunzhen Shi, Xing Wang, Zhengying Pan, Yuqin Song, Jun Zhu
The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies. However, the precise mechanism of action of the drug remains to be fully elucidated. Tumor-infiltrating macrophages presented in the tumor microenvironment have been shown to promote development and progression of B-cell lymphomas through crosstalk mediated by secreted cytokines and chemokines. Because Btk has been implicated in Toll-like receptor (TLR) signaling pathways that regulate macrophage activation and production of proinflammatory cytokines, we investigated the immunomodulatory effects of Btk inhibitor on macrophages...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424289/disruption-of-mda5-mediated-innate-immune-responses-by-the-3c-proteins-of-coxsackievirus-a16-coxsackievirus-a6-and-enterovirus-d68
#6
Yajuan Rui, Jiaming Su, Hong Wang, Junliang Chang, Shaohua Wang, Wenwen Zheng, Yong Cai, Wei Wei, James T Gordy, Richard Markham, Wei Kong, Wenyan Zhang, Xiao-Fang Yu
Coxsackievirus A16 (CV-A16), A6 (CV-A6), and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C(pro) proteins from CV-A16, CV-A6, and EV-D68 bind MDA5 and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I IFN signaling in the RLR pathway was blocked by CV-A16, CV-A6, and EV-D68 3C(pro) Furthermore, CV-A16, CV-A6, and EV-D68 3C(pro) all cleave TAK1, resulting in inhibition of NF-κB activation, a host response also critical for toll-like receptor (TLR) mediated signaling...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28422714/toll-like-receptor-3-as-an-immunotherapeutic-target-for-kras-mutated-colorectal-cancer
#7
Radhashree Maitra, Titto Augustine, Yitzchak Dayan, Carol Chandy, Matthew Coffey, Sanjay Goel
New therapeutic interventions are essential for improved management of patients with metastatic colorectal cancer (mCRC). This is especially critical for those patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all patients). This patient cohort is excluded from receiving anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical development for patients with chemotherapy refractory KRAS mutated tumors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421541/systemic-inflammation-as-a-driver-of-brain-injury-the-astrocyte-as-an-emerging-player
#8
Bruna Bellaver, João Paulo Dos Santos, Douglas Teixeira Leffa, Larissa Daniele Bobermin, Paola Haack Amaral Roppa, Iraci Lucena da Silva Torres, Carlos-Alberto Gonçalves, Diogo Onofre Souza, André Quincozes-Santos
Severe systemic inflammation has strong effects on brain functions, promoting permanent neurocognitive dysfunction and high mortality rates. Additionally, hippocampal damage seems to be directly involved in this process and astrocytes play an important role in neuroinflammation and in the neuroimmune response. However, the contribution of the astrocytes to the pathology of acute brain dysfunction is not well understood. Recently, our group established a protocol for obtaining astrocyte cultures from mature brain to allow the characterization of these cells and their functions under pathologic conditions...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421187/subset-specific-expression-of-toll-like-receptors-by-bovine-afferent-lymph-dendritic-cells
#9
Dirk Werling, Jayne C Hope, Nazneen Siddiqui, Stephanie Widdison, Chris Russell, Paul Sopp, Tracey J Coffey
Within the ruminant system, several possibilities exist to generate dendritic cells migrating out from the tissue into the regional draining lymph nodes as afferent lymph dendritic cells (ALDCs). Here, we analyzed toll-like receptor (TLR) 1-10 mRNA expression by using quantitative real-time PCR in highly purified subsets of bovine ALDC. As TLR expression may be influenced by pathogens or vaccines and their adjuvant, it is necessary to understand what TLRs are expressed in a steady-state system to elucidate specific differences and to potentially optimize targeted vaccines...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28418096/expression-of-toll-like-receptors-in-t-lymphocytes-stimulated-with-n-3-oxododecanoyl-l-homoserine-lactone-from-pseudomonas-aeruginosa
#10
Lei Bao, Jialin Yu, Haiying Zhong, Daochao Huang, Qi Lu
The establishment of chronic Pseudomonas aeruginosa infections is correlated with the disturbance of the host immune system. The P. aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL) has the potential to modulate the host immune system. The immune system recognizes pathogens via toll-like receptors (TLRs). We found that 3-O-C12-HSL induced TLR changes in monocytes. However, the role of T cells in P. aeruginosa infection has not been delineated. In order to understand this activity, we examined whether 3-O-C12-HSL has an effect on the immune function and the expression of TLRs in T lymphocytes...
April 18, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28418003/toll-like-receptor-polymorphisms-compromise-the-inflammatory-response-against-bacterial-antigen-translocation-in-cirrhosis
#11
Paula Piñero, Oriol Juanola, Esther Caparrós, Pedro Zapater, Paula Giménez, José M González-Navajas, José Such, Rubén Francés
Bacterial translocation is associated with clinically relevant complications in cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the soluble response against these episodes. Consecutive patients with cirrhosis and ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9 rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide, bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified in serum samples. In vitro response against specific ligands in variant TLR genotypes was evaluated...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417961/high-throughput-sequencing-and-co-expression-network-analysis-of-lncrnas-and-mrnas-in-early-brain-injury-following-experimental-subarachnoid-haemorrhage
#12
Jianhua Peng, Yue Wu, Xiaocui Tian, Jinwei Pang, Li Kuai, Fang Cao, Xinghu Qin, Jianjun Zhong, Xinshen Li, Yong Li, Xiaochuan Sun, Ligang Chen, Yong Jiang
Subarachnoid haemorrhage (SAH) is a fatal neurovascular disease following cerebral aneurysm rupture with high morbidity and mortality rates. Long non-coding RNAs (lncRNAs) are a type of mammalian genome transcript, are abundantly expressed in the brain and are involved in many nervous system diseases. However, little is currently known regarding the influence of lncRNAs in early brain injury (EBI) after SAH. This study analysed the expression profiles of lncRNAs and mRNAs in SAH brain tissues of mice using high-throughput sequencing...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416741/relaxin-abrogates-renal-interstitial-fibrosis-by-regulating-macrophage-polarization-via-inhibition-of-toll-like-receptor-4-signaling
#13
Lei Chen, Ming-Lei Sha, Deng Li, Yi-Ping Zhu, Xing-Jie Wang, Chen-Yi Jiang, Shu-Jie Xia, Yi Shao
Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit the CKD process, it is important to prevent renal fibrosis, though CKD remains incurable. Renal fibrosis can be inhibited by relaxin in several experimental models, but the mechanism of relaxin for antifibrotic potential is still not clear. And here we have studied the role of relaxin in macrophage polarization and renal inflammation after unilateral ureteral obstruction (UUO). Our results show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling, shift macrophage polarization toward the M2 phenotype and ameliorat renal fibrosis in the early stages of UUO...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414577/serum-toll-like-receptor-2-toll-like-receptor-4-levels-in-patients-with-hbeag-negative-chronic-viral-hepatitis-b
#14
Erdem Akbal, Erdem Koçak, Seyfettin Köklü, Bilal Ergül, Ömer Akyürek, Fatma Meriç Yılmaz
Toll-like receptors (TLRs) may play an important role in hepatitis-B pathogenesis. However, serum TLR-2 and TLR-4 levels and their association with serum liver enzymes, hepatitis B virus (HBV) DNA, quantitative HBsAg levels, and liver biopsy findings, are unknown. A total of naive 40 HBeAg (-) chronic hepatitis B (CHB) patients and 20 healthy control subjects were recruited in this study. Liver tests, HBV DNA, serum TLR-2 and TLR-4, and quantitative HBsAg levels were evaluated among all groups. The relationship among TLR-2, TLR-4, quantitative HBsAg levels and liver tests, and liver histological findings were investigated with correlation analysis...
April 17, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28413476/the-mechanism-of-human-%C3%AE-defensin-3-in-mrsa-induced-infection-of-implant-drug-resistant-bacteria-biofilm-in-the-mouse-tibial-bone-marrow
#15
Chen Zhu, Ni-Rong Bao, Shuo Chen, Jian-Ning Zhao
The mechanism of human β-defensin 3 (HBD-3) in methicillin-resistant Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague-Dawley rats with average weight of 230 g were selected to construct the infection model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left tibial bone marrow. The drugs were intraperitoneally injected after 24 h medullary cavity infection, and the experimental groups included the model group, HBD-3 group, and vancomycin group (20 rats in each group)...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28413475/evaluation-of-the-role-of-human-%C3%AE-defensin-3-in-modulation-of-immunity-and-inflammatory-response-after-knee-replacement
#16
Jiguang Jia, Hao Peng, Sen Chen
The present study investigated the value of human β-defensin 3 (HBD-3) in adjusting the immunity and inflammatory response of T lymphocytes in the body after knee replacement. Sixty-four cases of knee replacement patients were successively selected and randomly divided into the control group and the observation group each with 32 cases. Once a day, for 7 days, patients in the control group were injected with placebo saline solution in the articular cavity. Levels of Th1 and/Th2, interleukin (IL)-2 and IL-10, tumor necrosis factor (TNF)-α, toll-like receptor (TLR)-4, and alkaline phosphatase (ALP) were compared one month later, and implant infection rates were compared within 1-year follow-up...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28410580/lactobacillus-casei-dg-and-its-postbiotic-reduce-the-inflammatory-mucosal-response-an-ex-vivo-organ-culture-model-of-post-infectious-irritable-bowel-syndrome
#17
Debora Compare, Alba Rocco, Pietro Coccoli, Debora Angrisani, Costantino Sgamato, Barbara Iovine, Umberto Salvatore, Gerardo Nardone
BACKGROUND: The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model. METHODS: Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB...
April 14, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28410380/interleukin-10-and-prostaglandin-e2-have-complementary-but-distinct-suppressive-effects-on-toll-like-receptor-mediated-dendritic-cell-activation-in-ovarian-carcinoma
#18
Eva Brencicova, Ann L Jagger, Hayley G Evans, Mirella Georgouli, Alex Laios, Steve Attard Montalto, Gautam Mehra, Jo Spencer, Ahmed A Ahmed, Shanti Raju-Kankipati, Leonie S Taams, Sandra S Diebold
Dendritic cells (DC) have the potential to instigate a tumour-specific immune response, but their ability to prime naïve lymphocytes depends on their activation status. Thus, for tumour immunotherapy to be effective, the provision of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is crucial in order to overcome immunosuppression associated with the tumour microenvironment. To address this, we investigated how ovarian carcinoma (OC)-associated ascites impedes activation of DC by TLR agonists...
2017: PloS One
https://www.readbyqxmd.com/read/28408069/tlr7-mediated-activation-of-xbp1-correlates-with-the-ifn%C3%AE-production-in-humans
#19
Claudia Beisel, Susanne Ziegler, Glòria Martrus Zapater, Anaïs Chapel, Morgane Griesbeck, Heike Hildebrandt, Ansgar W Lohse, Marcus Altfeld
The transcription factor X-box binding protein 1 (XBP1) represents a key component of the endoplasmatic reticulum (ER) stress response and is required for the production of several pro-inflammatory cytokines. XBP1 is furthermore essential for the development and survival of plasmacytoid dendritic cells (pDCs), and has recently been suggested to be involved in toll-like receptor (TLR) 2/4 signaling. Activation of TLR7 on pDCs results in an upregulation of pro-inflammatory cytokines, such as type I interferons (IFN-I), and has been implicated in several autoimmune and inflammatory diseases, but the role of XBP1 in this process remains unknown...
April 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28407632/hypothermic-neuronal-rescue-from-infection-sensitised-hypoxic-ischaemic-brain-injury-is-pathogen-dependent
#20
Mari Falck, Damjan Osredkar, Elke Maes, Torun Flatebø, Thomas Ragnar Wood, Hemmen Sabir, Marianne Thoresen
Perinatal infection increases the vulnerability of the neonatal brain to hypoxic-ischaemic (HI) injury. Hypothermia treatment (HT) does not provide neuroprotection after pre-insult inflammatory sensitisation by lipopolysaccharide (LPS), a gram-negative bacterial wall constituent. However, early-onset sepsis in term babies is caused by gram-positive species in more than 90% of cases, and neuro-inflammatory responses triggered through the gram-negative route (Toll-like receptor 4, TLR-4) are different from those induced through the gram-positive route via TLR-2...
April 14, 2017: Developmental Neuroscience
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