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https://www.readbyqxmd.com/read/29241030/expression-profiles-of-genes-involved-in-tlrs-and-nlrs-signaling-pathways-of-water-buffaloes-infected-with-fasciola-gigantica
#1
Fu-Kai Zhang, Jun-Ling Hou, Ai-Jiang Guo, Ai-Ling Tian, Zhao-An Sheng, Wen-Bin Zheng, Wei-Yi Huang, Hany M Elsheikha, Xing-Quan Zhu
Infection of ruminants and humans with Fasciola gigantica is attracting increasing attention due to its economic impact and public health significance. However, little is known of innate immune responses during F. gigantica infection. Here, we investigated the expression profiles of genes involved in Toll-like receptors (TLRs) and NOD-like receptors (NLRs) signaling pathways in buffaloes infected with 500F. gigantica metacercariae. Serum, liver and peripheral blood mononuclear cell (PBMC) samples were collected from infected and control buffaloes at 3, 10, 28, and 70days post infection (dpi)...
December 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29236160/ethanol-and-cytokines-in-the-central-nervous-system
#2
Marisa Roberto, Reesha R Patel, Michal Bajo
The innate immune system plays a critical role in the ethanol-induced neuroimmune response in the brain. Ethanol initiates the innate immune response via activation of the innate immune receptors Toll-like receptors (TLRs, e.g., TLR4, TLR3, TLR7) and NOD-like receptors (inflammasome NLRs) leading to a release of a plethora of chemokines and cytokines and development of the innate immune response. Cytokines and chemokines can have pro- or anti-inflammatory properties through which they regulate the immune response...
December 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29222615/knockdown-expression-of-il-10r%C3%AE-gene-inhibits-prrsv-replication-and-elevates-immune-responses-in-pbmcs-of-tibetan-pig-in-vitro
#3
Yihui Chen, Ye Wang, Kai Zeng, Yun-Feng Lei, Xiao-Hui Chen, San-Cheng Ying, Xue-Bin Lv, Zezhou Wang, Rong Gao
Increase of interleukin-10 (IL-10) induced by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection has been intensely studied to inhibit the anti-viral responses of host pigs. Blockade of expression of IL-10 receptor (IL-10R) by RNA interference (RNAi) may relieve the immunosuppression caused by excessive IL-10 in PRRSV infection. The recombinant short hairpin expressing plasmid targeted to pig IL-10Rα was transfected into peripheral blood mononuclear cells of Tibetan pig (Tp-PBMCs) prior to PRRSV inoculation, then the replication of PRRSV and immune responses in Tp-PBMCs were evaluated...
December 8, 2017: Veterinary Research Communications
https://www.readbyqxmd.com/read/29220721/novel-effect-of-methionine-enkephalin-against-influenza-a-virus-infection-through-inhibiting-tlr7-myd88-traf6-nf-%C3%AE%C2%BAb-p65-signaling-pathway
#4
Jing Tian, Xue Jiao, Xiaonan Wang, Jin Geng, Reizhe Wang, Ning Liu, Xinhua Gao, Noreen Griffin, Fengping Shan
The morbidity and mortality associated with influenza A virus infections, have stimulated the search for novel prophylactic and therapeutic drugs. The purpose of this study was to investigate the prophylactic and therapeutic effect of synthetic methionine enkephalin (MENK) on mice infected by A/PR/8/34 influenza virus (H1N1) in vivo. The results showed that MENK could exert both prophylactic and therapeutic influences on infected mice, significantly improve the survival rate, relieve acute lung injury and decrease cytokine (IFN-α, IFN-β, TNF-α, IL-6, and IL-1β) levels...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29204451/targeting-of-immune-cells-by-dual-tlr2-7-ligands-suppresses-features-of-allergic-th2-immune-responses-in-mice
#5
Jonathan Laiño, Andrea Wangorsch, Frank Blanco, Sonja Wolfheimer, Maren Krause, Adam Flaczyk, Tobias-Maximilian Möller, Mindy Tsai, Stephen Galli, Stefan Vieths, Masako Toda, Stephan Scheurer, Stefan Schülke
Background: TLR ligands can promote Th1-biased immune responses, mimicking potent stimuli of viruses and bacteria. Aim: To investigate the adjuvant properties of dual TLR2/7 ligands compared to those of the mixture of both single ligands. Methods: Dual TLR2/7 ligands: CL401, CL413, and CL531, including CL264 (TLR7-ligand) and Pam2CysK4 (TLR2-ligand), were used. Immune-modulatory capacity of the dual ligands with the individual ligands alone or as a mixture in mouse BMmDCs, BMmDC:TC cocultures, or BMCMCs was compared and assessed in naïve mice and in a mouse model of OVA-induced intestinal allergy...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29200306/self-assembled-ligands-targeting-tlr7-a-molecular-level-investigation
#6
Marco A Deriu, Michela Cangiotti, Gianvito Grasso, Ginevra Licandro, Afsaneh Lavasanifar, Jack A Tuszynski, Maria Francesca Ottaviani, Andrea Danani
Toll-like Receptors (TLRs) are pattern recognition transmembrane proteins that play an important role in innate immunity. In particular, TLR7 plays a role in detecting nucleic acids derived from viruses and bacteria. The huge number of pathologies in which TLR7 is involved has led to an increasing interest in developing new compounds targeting this protein. Several conjugation strategies were proposed for TLR7 agonists to increase the potency while maintaining a low toxicity. In this work, we focus the attention on two promising classes of TLR7 compounds derived from the same pharmacophore conjugated with phospholipid and polyethylene glycol (PEG), respectively...
December 4, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29190907/profile-of-differentially-expressed-toll-like-receptor-signaling-genes-in-the-natural-killer-cells-of-patients-with-s%C3%A3-zary-syndrome
#7
Kelly C G ManfrereC, Marina P Torrealba, Denis R Miyashiro, Nátalli Z Pereira, Fabio S Y Yoshikawa, Luana de M Oliveira, Jade Cury-Martins, Alberto J S Duarte, José A Sanches, Maria N Sato
Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29185473/the-systemic-response-to-topical-aldara-treatment-is-mediated-through-direct-tlr7-stimulation-as-imiquimod-enters-the-circulation
#8
Louis Nerurkar, Alison McColl, Gerard Graham, Jonathan Cavanagh
Topical application of Aldara cream, containing the Toll-like receptor 7/8 agonist Imiquimod, is a widely used mouse model for investigating the pathogenesis of psoriasis. We have previously used this model to study the effects of peripheral inflammation on the brain, and reported a brain-specific response characterised by increased transcription, infiltration of immune cells and anhedonic-like behavior. Here, we perform a more robust characterisation of the systemic response to Aldara application and find a potent but transient response in the periphery, followed by a prolonged response in the brain...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29181417/toll-like-receptor-ligand-induced-liver-injury-in-d-galactosamine-sensitized-mice-differences-between-tlr7-8-and-tlr9-ligands-cytokine-patterns-and-cross-tolerance-induction-by-tlr2-ligand-pretreatment
#9
Reiko Seki
Administration of Toll-like receptor ligands (TLRLs) is known to cause liver injury in D-galN-sensitized mice. In the present study, we aimed to complement preceding reports on the TLRL/D-galN system by analyzing comparisons among TLRLs, mouse strain dependence, effects on serum levels of cytokines, and effects of sequential administrations of different TLRLs. In a preliminary set of analyses, we first confirmed that liver failure can be induced by diverse TLRLs, including LTA and R848 in combination with D-galN...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29181003/the-human-associated-archaeon-methanosphaera-stadtmanae-is-recognized-through-its-rna-and-induces-tlr8-dependent-nlrp3-inflammasome-activation
#10
Tim Vierbuchen, Corinna Bang, Hanna Rosigkeit, Ruth A Schmitz, Holger Heine
The archaeon Methanosphaera stadtmanae is a member of the gut microbiota; yet, the molecular cross-talk between archaea and the human immune system and its potential contribution to inflammatory diseases has not been evaluated. Although archaea are as bacteria prokaryotes, they form a distinct domain having unique features such as different cell wall structures and membrane lipids. So far, no microbe-associated molecular patterns of archaea which activate innate immune receptors have been identified. By stimulating human myeloid cells with M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29177921/inhibitory-effects-and-related-molecular-mechanisms-of-total-flavonoids-in-mosla-chinensis-maxim-against-h1n1-influenza-virus
#11
Xiao-Xia Zhang, Qiao-Feng Wu, Yun-Liang Yan, Feng-Ling Zhang
OBJECTIVE: The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. METHODS: The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF...
November 24, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29176742/tlr7-a-third-signal-for-the-robust-generation-of-spontaneous-germinal-center-b-cells-in-systemic-lupus-erythematosus
#12
Hongye Fan, Deshan Ren, Yayi Hou
No abstract text is available yet for this article.
November 27, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29174504/intravesical-immunomodulatory-imiquimod-enhances-bacillus-calmette-gu%C3%A3-rin-downregulation-of-nonmuscle-invasive-bladder-cancer
#13
Juliana A Camargo, Gabriela R Passos, Karen L Ferrari, Athanase Billis, Mário J A Saad, Leonardo O Reis
BACKGROUND: The Toll-like receptor (TLR)2/4 agonist bacillus Calmette-Guérin (BCG), although not failure proof, has been the most efficient immunomodulatory treatment of immunogenic nonmuscle-invasive bladder cancer (NMIBC) for > 40 years. We investigated the role of the immunomodulatory molecule TLR7 agonist imiquimod through the BCG key receptors TLR2/4 and the main downstream molecules of the mammalian target of rapamycin pathway in NMIBC treatment. MATERIALS AND METHODS: A total of 40 Fischer-344 rats, 7 weeks old, received 4 doses of 1...
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29170511/t-cell-targeting-nanoparticles-focus-delivery-of-immunotherapy-to-improve-antitumor-immunity
#14
Daniela Schmid, Chun Gwon Park, Christina A Hartl, Nikita Subedi, Adam N Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J Freeman, Kai W Wucherpfennig, Darrell J Irvine, Michael S Goldberg
Targeted delivery of compounds to particular cell subsets can enhance therapeutic index by concentrating their action on the cells of interest. Because attempts to target tumors directly have yielded limited benefit, we instead target endogenous immune cell subsets in the circulation that can migrate actively into tumors. We describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in the circulation and tumor...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163495/human-cd141-dendritic-cell-and-cd1c-dendritic-cell-undergo-concordant-early-genetic-programming-after-activation-in-humanized-mice-in-vivo
#15
Yoshihito Minoda, Isaac Virshup, Ingrid Leal Rojas, Oscar Haigh, Yide Wong, John J Miles, Christine A Wells, Kristen J Radford
Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34(+) hematopoietic stem cells. These "humanized" mice are useful models to study human immunology and human-tropic infections, autoimmunity, and cancer. However, some human immune cell subsets are unable to fully develop or acquire full functional capacity due to a lack of cross-reactivity of many growth factors and cytokines between species. Conventional dendritic cells (cDCs) in mice are categorized into cDC1, which mediate T helper (Th)1 and CD8(+) T cell responses, and cDC2, which mediate Th2 and Th17 responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158790/synergy-of-purine-scaffold-tlr7-agonist-with-doxorubicin-on-systemic-inhibition-of-lymphoma-in-mouse-model
#16
Dong Gao, Wang Li, Wanmin Wang, Yongguang Cai, Yuhuan Wang, Xiaoling Luo, Chih-Chang Wei
Chemo- and radio-therapy suffer from certain well-recognized drawbacks for lymphoma therapy. Passive immunotherapy with monoclonal antibody has improved outcome for patients with CD20(+) B cell lymphoma, but not for T cell lymphoma. Therefore, novel treatment approaches are clearly required for T cell lymphoma. To date, the combined application targeting TLR7, 8 and 9 has established long-term antitumor immunity. We previously synthesized a purine-scaffold TLR7 agonist named GD5. Here, we report that the intratumoral administration of GD5 combined with doxorubicin (DOX), a conventional chemotherapeutic agent in T cell lymphoma...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29157965/polymer-based-nanoparticles-loaded-with-a-tlr7-ligand-to-target-the-lymph-node-for-immunostimulation
#17
Jérôme Widmer, Cédric Thauvin, Inès Mottas, Van N'guyen, Florence Delie, Eric Allémann, Carole Bourquin
Small-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective for the immunotherapy of skin cancer when used as topical agents. Their systemic use has however been largely unsuccessful due to dose-limiting toxicity. We propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, to the lymph node in order to focus the immunostimulatory activity and to prevent a generalized inflammatory response. We demonstrate successful encapsulation of resiquimod in methoxypoly(ethylene glycol)-b-poly(DL-lactic acid) (mPEG-PLA) and mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles...
November 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29155428/small-molecule-inhibition-of-tlr8-through-stabilization-of-its-resting-state
#18
Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das, Jing Li, Kentaro Sakaniwa, Jin Jin, Yanyan Bian, Umeharu Ohto, Toshiyuki Shimizu, Hang Yin
Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and DNA molecular patterns. Nonetheless, few small molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation...
November 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29152879/y-rna-derived-small-rnas-in-sj%C3%A3-gren-s-syndrome-candidate-biomarkers
#19
Jayakanthan Kabeerdoss, Pulukool Sandhya, Debashish Danda
Anti-Ro and anti-La antibodies are important in pathogenesis and diagnosis of Sjögren's syndrome (SS). Ro60, Ro52 and La are RNA binding proteins of Y RNA, which were discovered more than three decades ago. Significance of Y RNA is not appreciated as much as Ro and La in SS. It can be hypothesised that 5'-YsRNA, short fragment derived from Y RNA may be recognized by TLR7 in pDC, which induces type I interferon signature in SS. New genomics tools, namely RNA seq, enables assay of 5'-YsRNA in blood. 5'-YsRNA has the potential to be a novel biomarker of SS...
November 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29152046/design-and-synthesis-of-n1-modified-imidazoquinoline-agonists-for-selective-activation-of-toll-like-receptors-7-and-8
#20
Peter Larson, Tamara A Kucaba, Zhengming Xiong, Michael Olin, Thomas S Griffith, David M Ferguson
A series of N1-modified imidazoquinolines were synthesized and screened for Toll-like receptors (TLR) 7 and 8 activities to identify recognition elements that confer high affinity binding and selectivity. These receptors are key targets in the development of immunomodulatory agents that signal the NF-κB mediated transcription of pro-inflammatory chemokines and cytokines. Results are presented showing both TLR7/8 activations are highly correlated to N1-substitution, with TLR8 selectivity achieved through inclusion of an ethyl-, propyl-, or butylamino group at this position...
November 9, 2017: ACS Medicinal Chemistry Letters
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