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Toll—like receptor

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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/28432254/tlr4-defective-c3h-hej-mice-are-not-protected-from-cast-immobilization-induced-muscle-atrophy
#2
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/28432091/suppressive-effects-of-tnf%C3%AE-il6-and-macrophages-on-thecal-androgen-production
#3
Moafaq S Samir, Claire Glister, Dareen Mattar, Mhairi Laird, Philip G Knight
Pro-inflammatory cytokines secreted by macrophages and other cell-types are implicated as intra-ovarian factors affecting different aspects of ovarian function including follicle and corpus luteum 'turnover', steroidogenesis and angiogenesis. Here, we compared granulosal (GC) and thecal (TC) expression of TNF, IL6 and their receptors (TNFR1, TNFRSF1B, IL6R) during bovine antral follicle development; all five mRNA transcripts were detected in both GC and TC and statistically significant cell-type and follicle stage-related differences were evident...
April 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28432060/toll-like-receptor-2-tlr2-dominance-over-tlr4-in-stressful-conditions-for-its-detrimental-role-in-the-heart
#4
Ashim K Bagchi, Gauri Akolkar, Soma Mandal, Prathapan Ayyappan, Xi Yang, Pawan K Singal
It has been suggested that toll-like receptor 4 (TLR4) promotes interleukin-10 (IL-10)-mediated cardiac cell survival while another receptor, TLR2, from the same family is detrimental. Here we examined the interactive role of these two innate signaling molecules under stressful conditions including interleukin-10 knockout (IL-10(-/-)) mice, global ischemia/reperfusion (I/R) injury in rat hearts and in-vitro shRNA experimental models in presence or absence of IL-10 (10ng/ml). Circulating and myocardial levels of tumor necrosis factor-α (TNF-α) as well as apoptosis and fibrosis were higher in IL-10(-/-) mice...
April 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28431901/clozapine-reduces-toll-like-receptor-4-nf-%C3%AE%C2%BAb-mediated-inflammatory-responses-through-inhibition-of-calcium-calmodulin-dependent-akt-activation-in-microglia
#5
Seunghyun Jeon, Se Hyun Kim, Soon Young Shin, Young Han Lee
Clozapine is an atypical antipsychotic agent used in the treatment of schizophrenia and severe mood disorders. Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of various neurodegenerative diseases and psychiatric disorders. Clozapine exerts anti-inflammatory activity. However, the molecular mechanism underlying the anti-inflammatory activity of clozapine is poorly understood. In this study, we found that clozapine suppressed lipopolysaccharide (LPS)-induced phosphorylation of IκBα at Ser-32 and of p65/RelA at Ser-468, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent transcriptional activity in microglial cells...
April 18, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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
#6
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/28430694/iron-loading-exaggerates-the-inflammatory-response-to-the-toll-like-receptor-4-ligand-lipopolysaccharide-by-altering-mitochondrial-homeostasis
#7
Konrad Hoeft, Donald B Bloch, Jan A Graw, Rajeev Malhotra, Fumito Ichinose, Aranya Bagchi
BACKGROUND: Perioperative and critically ill patients are often exposed to iron (in the form of parenteral-iron administration or blood transfusion) and inflammatory stimuli, but the effects of iron loading on the inflammatory response are unclear. Recent data suggest that mitochondrial reactive oxygen species have an important role in the innate immune response and that increased mitochondrial reactive oxygen species production is a result of dysfunctional mitochondria. We tested the hypothesis that increased intracellular iron potentiates lipopolysaccharide-induced inflammation by increasing mitochondrial reactive oxygen species levels...
April 21, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28429728/a-formulated-tlr7-8-agonist-is-a-flexible-highly-potent-and-effective-adjuvant-for-pandemic-influenza-vaccines
#8
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
#9
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/28428684/innate-immunity-of-adipose-tissue-in-rodent-models-of-local-and-systemic-staphylococcus-aureus-infection
#10
Andreas Schmid, Thomas Karrasch, Miriam Thomalla, Jutta Schlegel, Bernd Salzberger, Andreas Schäffler, Frank Hanses
Background. The role of adipose tissue in systemic inflammation during bacterial infection is unclear. Effects of Staphylococcus aureus infection on adipocytes in rodent models of experimental endocarditis and peritonitis, the impact of S. aureus infection on gene expression in epididymal and subcutaneous adipose tissue, and effects of S. aureus infection on the toll-like receptor-2- (TLR2-) cathelicidin pathway in vivo and in vitro were investigated. Material and methods. The rat model of catheter-induced S...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28428349/toll-like-receptor-4-mediates-hemorrhagic-transformation-after-delayed-tissue-plasminogen-activator-administration-in-in-situ-thromboembolic-stroke
#11
Alicia García-Culebras, Sara Palma-Tortosa, Ana Moraga, Isaac García-Yébenes, Violeta Durán-Laforet, Maria I Cuartero, Juan de la Parra, Ana L Barrios-Muñoz, Jaime Díaz-Guzmán, Jesús M Pradillo, María A Moro, Ignacio Lizasoain
BACKGROUND AND PURPOSE: Hemorrhagic transformation is the main complication of revascularization therapies after stroke. Toll-like receptor 4 (TLR4) is implicated in cerebral damage and inflammation in stroke. This study was designed to determine the role of TLR4 in hemorrhagic transformation development after tissue plasminogen activator (tPA) administration. METHODS: Mice expressing (TLR4(+/+)) or lacking functional TLR4 (TLR4(-)(/-)) were subjected to middle cerebral artery occlusion using an in situ thromboembolic model by thrombin injection into the middle cerebral artery, and tPA (10 mg/kg) was administered 20 minutes or 3 hours after ischemia...
April 20, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28427951/uncovering-the-immune-responses-of-apis-mellifera-ligustica-larval-gut-to-ascosphaera-apis-infection-utilizing-transcriptome-sequencing
#12
Dafu Chen, Rui Guo, Xijian Xu, Cuiling Xiong, Qin Liang, Yanzhen Zheng, Qun Luo, Zhaonan Zhang, Zhijian Huang, Dhiraj Kumar, Weijun Xi, Xuan Zou, Min Liu
Honeybees are susceptible to a variety of diseases, including chalkbrood, which is capable of causing huge losses of both the number of bees and colony productivity. This research is designed to characterize the transcriptome profiles of Ascosphaera apis-treated and un-treated larval guts of Apis mellifera ligustica in an attempt to unravel the molecular mechanism underlying the immune responses of western honeybee larval guts to mycosis. In this study, 24, 296 and 2157 genes were observed to be differentially expressed in A...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28427896/toll-like-receptor-2-an-important-immunomodulatory-molecule-during-helicobacter-pylori-infection
#13
REVIEW
Maryam Nemati, Tiziana Larussa, Hossein Khorramdelazad, Merat Mahmoodi, Abdollah Jafarzadeh
Toll like receptors (TLRs) are an essential subset of pathogen recognition receptors (PRRs) which identify the microbial components and contribute in the regulation of innate and adaptive immune responses against the infectious agents. The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of immune response against H. pylori. TLR2 is expressed on a number of immune and non-immune cells and recognizes a vast broad of microbial components due to its potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10...
April 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28427050/expression-of-high-mobility-group-protein-b1-in-cardiac-tissue-of-elderly-patients-with-coronary-artery-disease-with-or-without-inflammatory-rheumatic-disease
#14
Mei Bruton, Ivana Hollan, Julie Xiao, Eva Lindroos, Knut Mikkelsen, Stein E Rynning, Kjell Saatvedt, Sven M Almdahl, Helena E Harris, Ingrid E Lundberg, Cecilia Wick
BACKGROUND: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes...
April 21, 2017: Gerontology
https://www.readbyqxmd.com/read/28427048/1-25-dihydroxyvitamin-d3-attenuates-the-effects-of-lipopolysaccharide-by-causing-adam10-dependent-ectodomain-shedding-of-toll-like-receptor-4
#15
Won Seok Yang, Jin Ju Kim, Nam Jeong Han, Eun Kyoung Lee, Su-Kil Park
BACKGROUND/AIMS: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits the effects of lipopolysaccharide (LPS) in human aortic endothelial cells. METHODS: Cellular signaling was explored by determination of protein abundance with Western blot, measurement of cytosolic Ca2+ concentration and immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10). RESULTS: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM-1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen-activated protein kinase (p38 MAPK)...
April 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#16
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/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#17
Yu Shanshan, Jiang Beibei, Tan Li, Gao Minna, Lei Shipeng, Peng Li, Zhao Yong
Microglia-mediated inflammation is an important step in the progression of cerebral ischemia/reperfusion injury and the associated production of receptors of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6 (Prdx6) has been demonstrated as the endogenous antioxidant protein for its peroxidase properties. However, the role of the independent phospholipase A2 (iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33) would have a critical effect on inflammatory brain damage...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28424490/direct-recognition-of-lps-drive-tlr4-expressing-cd8-t-cell-activation-in-patients-with-rheumatoid-arthritis
#18
Archana Tripathy, Shweta Khanna, Prasanta Padhan, Shuchi Smita, Sunil Raghav, Bhawna Gupta
Aberrant immune responses characterize autoimmune disorders like Rheumatoid Arthritis (RA) wherein lymphocytes are recognized as key players. Role of CD8(+) T cells in RA has been less defined however we found that these cells are activated in RA patients with increased expression of cytolytic granules and inflammatory mediators thereby modulating immune responses contributing to disease severity. Though unconventional expression of different Toll Like Receptors (TLRs) on CD8(+) T cells has been proposed but their expression and role in T cell activation and differentiation in RA still remains obscure...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424405/the-bruton-s-tyrosine-kinase-inhibitor-ibrutinib-exerts-immunomodulatory-effects-through-regulation-of-tumor-infiltrating-macrophages
#19
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
#20
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
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