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https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#1
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432355/basal-autophagy-prevents-autoactivation-or-enhancement-of-inflammatory-signals-by-targeting-monomeric-myd88
#2
Takeshi Into, Toshi Horie, Megumi Inomata, Jin Gohda, Jun-Ichiro Inoue, Yukitaka Murakami, Shumpei Niida
Autophagy, the processes of delivery of intracellular components to lysosomes, regulates induction of inflammation. Inducible macroautophagy degrades inflammasomes and dysfunctional mitochondria to downregulate inflammatory signals. Nonetheless, the effects of constitutive basal autophagy on inflammatory signals are largely unknown. Here, we report a previously unknown effect of basal autophagy. Lysosomal inhibition induced weak inflammatory signals in the absence of a cellular stimulus and in the presence of a nutrient supply, and their induction was impaired by MyD88 deficiency...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432254/tlr4-defective-c3h-hej-mice-are-not-protected-from-cast-immobilization-induced-muscle-atrophy
#3
Noriaki Kawanishi, Risa Nozaki, Hisashi Naito, Shuichi Machida
Recent studies have shown that activation of Toll-like receptor (TLR)4 signaling may be an important factor in muscle atrophy and excessive inflammatory response associated with immobilization. To examine the role of TLR4 signaling on cast immobilization-induced skeletal muscle atrophy, we tested the hypothesis that muscle atrophy and inflammation after cast immobilization is reduced in TLR4-defective mice. TLR4-defective (C3H/HeJ) and wild type (C3H/HeN) mice were divided into control and cast-immobilization groups...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28432147/cutting-edge-a-dual-tlr2-and-tlr7-ligand-induces-highly-potent-humoral-and-cell-mediated-immune-responses
#4
Alice Gutjahr, Laura Papagno, Francesco Nicoli, Alain Lamoureux, Fabienne Vernejoul, Thierry Lioux, Emma Gostick, David A Price, Gérard Tiraby, Eric Perouzel, Victor Appay, Bernard Verrier, Stéphane Paul
TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8(+) T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2 profile in mice...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#5
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
#6
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/28429188/18f-fluorodeoxyglucose-uptake-on-positron-emission-tomography-computed-tomography-is-associated-with-metastasis-and-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma
#7
Misu Lee, Jeong Yong Jeon, Micheal L Neugent, Jung-Whan Kim, Mijin Yun
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. Several studies have investigated the relationship between (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography and the prognosis of patients with HCC, although the relationship between (18)F-FDG uptake and expression of EMT-related proteins in these patients remains unclear. We retrospectively enrolled 116 patients with HCC treated by curative surgical resection and who underwent (18)F-FDG positron emission tomography/computed tomography (PET/CT) for preoperative staging...
April 20, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28428828/bioinformatics-analysis-of-key-genes-and-latent-pathway-interactions-based-on-the-anaplastic-thyroid-carcinoma-gene-expression-profile
#8
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/28426135/tlr-stimulated-eosinophils-mediate-recruitment-and-activation-of-nk-cells-in-vivo
#9
Shaunagh M O'Flaherty, Kripitch Sutummaporn, Walina L Häggtoft, Amy P Worrall, Marzia Rizzo, Viorica Braniste, Petter Höglund, Nadir Kadri, Benedict J Chambers
Eosinophils like many myeloid innate immune cells can provide cytokines and chemokines for the activation of other immune cells upon TLR stimulation. When TLR stimulated eosinophils were inoculated i.p. into wildtype mice, NK cells were rapidly recruited and exhibited anti-tumor cytotoxicity. However when mice depleted of CD11c(+) cells were used, a marked decrease in the number of recruited NK cells was observed. We postulated that CpG or LPS from the injected eosinophils could be transferred to host cells, which in turn could recruit NK cells...
April 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#10
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
#11
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
#12
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/28424222/randomized-comparison-of-paclitaxel-eluting-balloon-angioplasty-plus-stenting-versus-standard-balloon-angioplasty-plus-stenting-versus-directional-atherectomy-for-symptomatic-femoral-artery-disease-isar-stath
#13
Ilka Ott, Salvatore Cassese, Philipp Groha, Birgit Steppich, Martin Hadamitzky, Tareq Ibrahim, Sebastian Kufner, Karl Dewitz, Regina V Hiendlmayer, Karl-Ludwig Laugwitz, Heribert Schunkert, Adnan Kastrati, Massimiliano Fusaro
Background -Atherosclerosis in the superficial femoral artery (SFA) is common in patients suffering from peripheral artery disease. Paclitaxel-eluting balloon (PEB) angioplasty, stenting and directional atherectomy (DA) have provided new options for the treatment of SFA disease, however the comparative efficacy remains uncertain. Methods -One hundred and fifty five patients with symptomatic peripheral artery disease with de novo SFA stenotic or occlusive lesions were randomized to treatment with plain balloon angioplasty (BA) followed by PEB angioplasty and stenting (n=48), BA followed by stenting (n=52) or directional DA with distal protection and bailout stenting (n=55)...
April 19, 2017: Circulation
https://www.readbyqxmd.com/read/28422714/toll-like-receptor-3-as-an-immunotherapeutic-target-for-kras-mutated-colorectal-cancer
#14
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
#15
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/28421347/tu-100-exerts-a-protective-effect-against-bacterial-translocation-by-maintaining-the-tight-junction
#16
Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28421187/subset-specific-expression-of-toll-like-receptors-by-bovine-afferent-lymph-dendritic-cells
#17
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/28419983/pam3csk4-induces-mmp-9-expression-in-human-monocytic-thp-1-cells
#18
Fatema Al-Rashed, Shihab Kochumon, Safa Usmani, Sardar Sindhu, Rasheed Ahmad
BACKGROUND: Matrix metalloproteinase (MMP)-9 is known to degrade the extracellular matrix and increased MMP-9 levels are related with the pathogenesis of many inflammatory conditions including obesity. Pam3CSK4 is a synthetic triacylated lipopeptide (LP) which is a potent activator of immune cells and induces cytokine production. However, it is unclear whether Pam3CSK4 is able to induce MMP-9 expression in monocytic cells. We, therefore, determined MMP-9 production by Pam3CSK4-treated THP-1 cells and also investigated the signal transduction pathway(s) involved...
April 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28418842/effects-of-tlr-2-nf-%C3%AE%C2%BAb-signaling-pathway-on-the-occurrence-of-degenerative-knee-osteoarthritis-an-in-vivo-and-in-vitro-study
#19
Yi-Xun Liu, Guo-Dong Wang, Xiao Wang, Yong-Le Zhang, Tian-Lun Zhang
The study aims to explore the effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis (OA). Degenerative knee OA and normal cartilage samples were collected from patients with degenerative knee OA receiving total knee arthroplasty and amputation. Expressions of TLR-2, NF-κB and MMP-13 were determined by qRT-PCR and immunochemistry. The chondrocytes were divided into control, IL-1β, IL-1β + anti-TLR-2 and IL-1β + PDTC groups. MTT assay and flow cytometry were performed to determine proliferation and apoptosis of the chondrocytes...
March 15, 2017: Oncotarget
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
#20
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
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