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https://www.readbyqxmd.com/read/29215065/toll-like-receptor-activation-induces-degeneration-of-human-intervertebral-discs
#1
Emerson Krock, Derek H Rosenzweig, J Brooke Currie, Daniel G Bisson, Jean A Ouellet, Lisbet Haglund
Toll-like receptors (TLR) are activated by endogenous alarmins such as fragmented extracellular matrix compounds found in the degenerating disc. TLRs regulate cytokine, neurotrophin, and protease expression in human disc cells in vitro, and thus control key factors in disc degeneration. However, whether TLR activation leads to degenerative changes in intact human discs is unclear. Nucleus pulposus (NP) cells isolated from non-degenerating discs increase IL-1β and nerve growth factor gene expression following treatment with Pam2CSK4 (TLR2/6 agonist) but not Pam3CSK4 (TLR1/2 agonist)...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212908/naive-cd4-t-cells-carrying-a-tlr2-agonist-overcome-tgf-%C3%AE-mediated-tumor-immune-evasion
#2
Mohsen Ibrahim, Davide Scozzi, Kelsey A Toth, Donatella Ponti, Daniel Kreisel, Cecilia Menna, Elena De Falco, Antonio D'Andrilli, Erino A Rendina, Antonella Calogero, Alexander S Krupnick, Andrew E Gelman
TLR agonists are effective at treating superficial cancerous lesions, but their use internally for other types of tumors remains challenging because of toxicity. In this article, we report that murine and human naive CD4+ T cells that sequester Pam3Cys4 (CD4+ TPam3) become primed for Th1 differentiation. CD4+ TPam3 cells encoding the OVA-specific TCR OT2, when transferred into mice bearing established TGF-β-OVA-expressing thymomas, produce high amounts of IFN-γ and sensitize tumors to PD-1/programmed cell death ligand 1 blockade-induced rejection...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29211798/lipl21-lipoprotein-binding-to-peptidoglycan-enables-leptospira-interrogans-to-escape-nod1-and-nod2-recognition
#3
Gwenn Ratet, Ignacio Santecchia, Martine Fanton d'Andon, Frédérique Vernel-Pauillac, Richard Wheeler, Pascal Lenormand, Frédéric Fischer, Pierre Lechat, David A Haake, Mathieu Picardeau, Ivo G Boneca, Catherine Werts
Leptospirosis is a widespread zoonosis, potentially severe in humans, caused by spirochetal bacteria, Leptospira interrogans (L. interrogans). Host defense mechanisms involved in leptospirosis are poorly understood. Recognition of lipopolysaccharide (LPS) and lipoproteins by Toll-Like Receptors (TLR)4 and TLR2 is crucial for clearance of leptospires in mice, yet the role of Nucleotide Oligomerization Domain (NOD)-like receptors (NOD)1 and NOD2, recognizing peptidoglycan (PG) fragments has not previously been examined...
December 6, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29201195/anti-nociceptive-effect-of-dexmedetomidine-in-a-rat-model-of-monoarthritis-via-suppression-of-the-tlr4-nf-%C3%AE%C2%BAb-p65-pathway
#4
Dong Ji, Yalan Zhou, Shuangshuang Li, Dai Li, Hui Chen, Yuanchang Xiong, Yuqiu Zhang, Hua Xu
As a therapeutic target for neuropathic pain, the anti-nociceptive effects of α 2-adrenoceptors (α2AR) have attracted attention. Dexmedetomidine (DEX), a potent and highly selective α2AR agonist, has exhibited significant analgesic effects in neuropathic pain, but the underlying mechanism has remained elusive. The present study investigated the effect of DEX on Toll-like receptor (TLR)4 and nuclear factor (NF)-κB p65 expression, as well as the production of pro-inflammatory cytokines. The rat monoarthritis (MA) model was induced by intra-articular injection of complete Freund's adjuvant (CFA) at the ankle joint...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29198126/effect-of-lipopolysaccharide-on-toll-like-receptor-4-signals-in-mouse-cancer-cells
#5
N Dana, S H Javanmard, G Vaseghi
BACKGROUND: Recent findings showed that activated TLR signals on cancer cells might promote cancer progression. This study was designed to explore the influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on mouse melanoma and breast cancer cell proliferation and their TLR4 signalling. METHODS: Mouse melanoma cell line (B16F10) and breast cancer cell line (4T1) were taken as models. They were treated with LPS (0, 1.25, 2.5, 5, 7.5, 10 µg/ml) for 4, 16, 24, 48 h and MTT assay was done...
2017: Bratislavské Lekárske Listy
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
#6
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/29187337/prr-signaling-during-in-vitro-macrophage-differentiation-from-progenitors-modulates-their-subsequent-response-to-inflammatory-stimuli
#7
Alba Martínez, Cristina Bono, Javier Megías, Alberto Yáñez, Daniel Gozalbo, M Luisa Gil
Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage in vitro and also in vivo following infection. In this study, we used an in vitro model of HSPC differentiation to investigate the functional consequences (cytokine production) that exposing HSPCs to various pathogen-associated molecular patterns (PAMPs) and Candida albicans cells have on the subsequently derived macrophages. Mouse HSPCs (Lin- cells) were cultured with GM-CSF to induce macrophage differentiation in the presence or absence of the following pattern recognition receptor (PRR) agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or inactivated C...
September 1, 2017: European Cytokine Network
https://www.readbyqxmd.com/read/29174504/intravesical-immunomodulatory-imiquimod-enhances-bacillus-calmette-gu%C3%A3-rin-downregulation-of-nonmuscle-invasive-bladder-cancer
#8
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/29172458/transiently-thermoresponsive-acetal-polymers-for-safe-and-effective-administration-of-amphotericin-b-as-vaccine-adjuvant
#9
Simon Van Herck, Lien Van Hoecke, Benoit Louage, Lien Lybaert, Ruben De Coen, Sabah Kasmi, Aaron P Esser-Kahn, Sunil A David, Lutz Nuhn, Bert Schepens, Xavier Saelens, Bruno G De Geest
The quest for new potent and safe adjuvants to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, Amphotericin B (AmpB) - an FDA-approved anti-fungal drug - has recently been discovered to possess TLR triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant...
November 26, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29170442/inhibition-of-the-inflammatory-response-to-stress-by-targeting-interaction-between-pkr-and-its-cellular-activator-pact
#10
Stephanie Dabo, Patrick Maillard, Milagros Collados Rodriguez, Marianne Doré Hansen, Sabrina Mazouz, Donna-Joe Bigot, Marion Tible, Geneviève Janvier, Olivier Helynck, Patricia Cassonnet, Yves Jacob, Jacques Bellalou, Anne Gatignol, Rekha C Patel, Jacques Hugon, Hélène Munier-Lehmann, Eliane F Meurs
PKR is a cellular kinase involved in the regulation of the integrative stress response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding Domains (DRBD) are required for activation of PKR, by interaction with either dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT in inflammatory processes linked to neurodegenerative diseases has been proposed and raised interest for pharmacological PKR inhibitors. However, the role of PKR in inflammation is subject to controversy...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157965/polymer-based-nanoparticles-loaded-with-a-tlr7-ligand-to-target-the-lymph-node-for-immunostimulation
#11
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/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#12
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29155256/role-of-toll-like-receptors-in-inflammatory-bowel-disease
#13
REVIEW
Nastaran Kordjazy, Arvin Haj-Mirzaian, Arya Haj-Mirzaian, Mohammad Mojtaba Rohani, Erwin W Gelfand, Nima Rezaei, Amir Hossein Abdolghaffari
Inflammatory bowel disease (IBD) is the chronic inflammation of the gastrointestinal tract. Recently, studies of the interplay between the adaptive and innate immune responses have provided a better understanding of the immunopathogenesis of inflammatory disorders such as IBD, as well as identification of novel targets for more potent interventions. Toll-like receptors (TLRs) are a class of proteins that play a significant role in the innate immune system and are involved in inflammatory processes. Activation of TLR signal transduction pathways lead to the induction of numerous genes that function in host defense, including those for inflammatory cytokines, chemokines, and antigen presenting molecules...
November 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29153953/inhibition-of-curcumin-on-influenza-a-virus-infection-and-influenzal-pneumonia-via-oxidative-stress-tlr2-4-p38-jnk-mapk-and-nf-%C3%AE%C2%BAb-pathways
#14
Jianping Dai, Liming Gu, Yun Su, Qianwen Wang, Ying Zhao, Xiaoxua Chen, Huixiong Deng, Weizhong Li, Gefei Wang, Kangsheng Li
Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID50, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo...
November 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29152046/design-and-synthesis-of-n1-modified-imidazoquinoline-agonists-for-selective-activation-of-toll-like-receptors-7-and-8
#15
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
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#16
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29141862/the-activation-of-human-dermal-microvascular-cells-by-poly-i-c-lipopolysaccharide-imiquimod-and-odn2395-is-mediated-by-the-fli1-foxo3a-pathway
#17
Lukasz Stawski, Grace Marden, Maria Trojanowska
Endothelial cell (EC) dysfunction has been associated with inflammatory and autoimmune diseases; however, the factors contributing to this dysfunction have not been fully explored. Because activation of TLRs has been implicated in autoimmune diseases, the goal of this study was to determine the effects of TLR ligands on EC function. Human dermal microvascular ECs (HDMECs) treated with TLR3 [Poly(I:C)], TLR4 (LPS), and TLR7 (imiquimod) agonists showed decreased proliferation and a reduced total number of branching tubules in three-dimensional human dermal organoid ex vivo culture...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29128406/recognition-of-candida-albicans-by-gingival-fibroblasts-the-role-of-tlr2-tlr4-cd14-and-myd88
#18
Claudia Ramos Pinheiro, Ana Lúcia Coelho, Carine Ervolino de Oliveira, Thaís Helena Gasparoto, Gustavo Pompermaier Garlet, João Santana Silva, Carlos Ferreira Santos, Karen Angélica Cavassani, Cory M Hogaboam, Ana Paula Campanelli
Recent evidence indicates that nonprofessional immune cells such as epithelial cells, endothelial cells, and fibroblasts also contribute to innate immunity via secretion of cytokines. Fibroblasts are the principal type of cell found in the periodontal connective tissues and they are involved in the immune response during periodontal disease. The role of fibroblasts in the recognition of pathogens via Toll-like receptors (TLRs) has been established; however, few studies have been conducted concerning the involvement of innate immune receptors in the recognition of Candida albicans by gingival fibroblast...
November 8, 2017: Cytokine
https://www.readbyqxmd.com/read/29123526/toll-like-receptor-ligands-and-interferon-%C3%AE-synergize-for-induction-of-antitumor-m1-macrophages
#19
Elisabeth Müller, Panagiotis F Christopoulos, Sanjib Halder, Anna Lunde, Kahsai Beraki, Martin Speth, Inger Øynebråten, Alexandre Corthay
Tumor-associated macrophages may either promote or suppress tumor growth depending on their activation status. Interferon-γ (IFN-γ) has been identified as a key factor for inducing tumoricidal M1 phenotype in macrophages. However, it remains unclear whether IFN-γ is sufficient or if additional stimuli are required. Here, we tested IFN-γ and a panel of toll-like receptor (TLR) agonists for the ability to activate murine macrophages toward a tumoricidal M1 phenotype. The following TLR ligands were used: TLR1/TLR2 agonist Pam3CSK4, TLR2/TLR6 agonist lipotechoic acid, TLR3 agonist poly(I:C), TLR4 agonist lipopolysaccharide (LPS), TLR5 agonist flagellin, TLR7 agonist CL264, and TLR9 agonist CpG...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29113797/caveolin-1-a-binding-protein-of-cd26-is-essential-for-the-anti-inflammatory-effects-of-dipeptidyl-peptidase-4-inhibitors-on-human-and-mouse-macrophages
#20
Munenori Hiromura, Kyoko Nohtomi, Yusaku Mori, Hideo Kataoka, Marika Sugano, Kei Ohnuma, Hirotaka Kuwata, Tsutomu Hirano
We previously reported that inhibition of dipeptidyl peptidase (DPP)-4, the catalytic site of CD26, prevents atherosclerosis in animal models through suppression of inflammation; however, the underlying molecular mechanisms have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae located on the surface of the cellular membrane, has been reported to modulate inflammatory responses by binding to CD26 in T cells. In this study, we investigated the role of Cav-1 in the suppression of inflammation mediated by the DPP-4 inhibitor, teneligliptin, using mouse and human macrophages...
November 4, 2017: Biochemical and Biophysical Research Communications
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