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https://www.readbyqxmd.com/read/28437629/design-and-development-of-benzoxazole-derivatives-with-toll-like-receptor-9-antagonism
#1
Swarnali Roy, Ayan Mukherjee, Barnali Paul, Oindrila Rahaman, Shounak Roy, Gundaram Maithri, Bandaru Ramya, Sourav Pal, Dipyaman Ganguly, Arindam Talukdar
Toll-like receptor 9 (TLR9) is a major therapeutic target for numerous inflammatory disorders. Development of small molecule inhibitors for TLR9 remains largely empirical due to lack of structural understanding of potential TLR9 antagonism by small molecules and due to the unusual topology of the ligand binding surface of the receptor. To develop a structural model for rational design of small molecule TLR9 antagonists, an enhanced homology model of human TLR9 (hTLR9) was constructed. Binding mode analysis of a series of molecules having characteristic molecular geometry, flexibility and basicity was conducted based on crystal structure of the inhibitory DNA (iDNA) bound to horse and bovine TLR9...
April 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433888/plasma-derived-exosomes-contribute-to-inflammation-via-the-tlr9-nf-%C3%AE%C2%BAb-pathway-in-chronic-heart-failure-patients
#2
Wei Ye, Xiaojun Tang, Zhengquan Yang, Chu Liu, Xin Zhang, Jing Jin, Jianxin Lyu
Exosomes are small vesicles that contain proteins, DNA and RNA, and play an important role in inflammation; however, the underlying mechanism remains unclear. In the present study, we found increased plasma-derived exosomes in chronic heart failure patients compared with healthy controls. Further, our data demonstrated that plasma-derived exosomes carried mtDNA, and triggered an inflammatory response via the TLR9-NF-κB pathway, as well, the inflammatory effect was closely related to exosomal mtDNA copy number...
April 20, 2017: Molecular Immunology
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
#3
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/28432035/expression-of-pattern-recognition-receptors-and-activation-of-the-non-canonical-inflammasome-pathway-in-brain-pericytes
#4
Ádám Nyúl-Tóth, Mihály Kozma, Péter Nagyőszi, Krisztina Nagy, Csilla Fazakas, János Haskó, Kinga Molnár, Attila E Farkas, Attila G Végh, György Váró, Péter Galajda, Imola Wilhelm, István A Krizbai
Cerebral pericytes are mural cells embedded in the basement membrane of capillaries. Increasing evidence suggests that they play important role in controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and permeability of the blood-brain barrier. These cells can also influence neuroinflammation which is highly regulated by the innate immune system. Therefore, we systematically tested the pattern recognition receptor expression of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5, NLRP9, NLRP10 and NLRX mRNA in non-treated cells...
April 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28427896/toll-like-receptor-2-an-important-immunomodulatory-molecule-during-helicobacter-pylori-infection
#5
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/28426135/tlr-stimulated-eosinophils-mediate-recruitment-and-activation-of-nk-cells-in-vivo
#6
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/28418003/toll-like-receptor-polymorphisms-compromise-the-inflammatory-response-against-bacterial-antigen-translocation-in-cirrhosis
#7
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/28410407/bacterial-amyloid-curli-acts-as-a-carrier-for-dna-to-elicit-an-autoimmune-response-via-tlr2-and-tlr9
#8
Sarah A Tursi, Ernest Y Lee, Nicole J Medeiros, Michael H Lee, Lauren K Nicastro, Bettina Buttaro, Stefania Gallucci, Ronald Paul Wilson, Gerard C L Wong, Çagla Tükel
Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is the amyloid curli, which forms highly immunogenic complexes with DNA. Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies. Here, we show that DNA complexed with amyloid curli powerfully stimulates Toll-like receptor 9 (TLR9) through a two-step mechanism...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28409518/colon-epithelial-injury-in-critically-ill-colectomized-patients-aberration-of-tight-junction-proteins-and-toll-like-receptors
#9
Seija Sipola, Tero I Ala-Kokko, Jouko J Laurila, Juha Saarnio, Pasi Ohtonen, Hannu Syrjälä, Tuomo J Karttunen
BACKGROUND: Abnormal permeability and extensive epithelial injury are characteristic of colon wall damage complicating critical illness, such as sepsis, and associated with mortality. To assess mechanisms of such colon epithelial disruption, we studied expression of markers of innate immunity and intercellular junctions in patients with critical illness. METHODS: Emergency colectomy samples from 38 intensive care unit patients with sepsis, fulminant C. difficile colitis, or colon ischemia were studied...
April 13, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28401895/integrated-host-and-viral-transcriptome-analyses-reveal-pathology-and-inflammatory-response-mechanisms-to-alv-j-injection-in-spf-chickens
#10
Xi Lan, Yan Wang, Kai Tian, Fei Ye, Huadong Yin, Xiaoling Zhao, Hengyong Xu, Yong Huang, Haibo Liu, John C F Hsieh, Susan J Lamont, Qing Zhu
Avian leukosis virus (ALV) is detrimental to poultry health and causes substantial economic losses from mortality and decreased performance. Because tumorigenesis is a complex mechanism, the regulatory architecture of the immune system is likely to include the added dimensions of modulation by miRNAs and long-noncoding RNA (lncRNA). To characterize the response to ALV challenge, we developed a novel methodology that combines four datasets: mRNA expression and the associated regulatory factors of miRNA and lncRNA, and ALV gene expression...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385547/in-vitro-and-in-vivo-stimulation-of-toll-like-receptor-9-by-cpg-oligodeoxynucleotides-incorporated-into-polypod-like-dna-nanostructures
#11
Yosuke Takahashi, Tatsuoki Maezawa, Yuki Araie, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
Cytosine-phosphate-guanine (CpG) DNA is known to increase the potency of vaccines. Here, in vitro and in vivo stimulation of Toll-like receptor 9 (TLR9) by CpG DNA incorporated into polypod-like DNA nanostructures was evaluated by measuring the levels of tumor necrosis factor alpha (TNF-α) released from macrophage-like RAW 264.7 cells and plasma interleukin (IL)-12p40 in vivo following intravenous injection into mice. Phosphodiester CpG1668 was selected as the CpG DNA, and tripodna and hexapodna, which were CpG1668-containing tripod and hexapod-like DNA nanostructures, respectively, were designed...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28382943/badger-macrophages-fail-to-produce-nitric-oxide-a-key-anti-mycobacterial-effector-molecule
#12
Kirstin Bilham, Amy C Boyd, Stephen G Preston, Christina D Buesching, Chris Newman, David W Macdonald, Adrian L Smith
The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373582/chronic-fibro-inflammatory-responses-in-autoimmune-pancreatitis-depend-on-ifn-%C3%AE-and-il-33-produced-by-plasmacytoid-dendritic-cells
#13
Tomohiro Watanabe, Kouhei Yamashita, Yasuyuki Arai, Kosuke Minaga, Ken Kamata, Tomoyuki Nagai, Yoriaki Komeda, Mamoru Takenaka, Satoru Hagiwara, Hiroshi Ida, Toshiharu Sakurai, Naoshi Nishida, Warren Strober, Masatoshi Kudo
In previous studies, we found that human IgG4-related autoimmune pancreatitis (AIP) and murine AIP are driven by activation of plasmacytoid dendritic cells (pDCs) producing IFN-α. In the present studies we examined additional roles of pDC-related mechanisms in AIP pathogenesis, particularly those responsible for induction of fibrosis. We found that in murine AIP (MRL/Mp mice treated with polyinosinic-polycytidylic acid) not only the pancreatic infiltration of immune cells but also the development of fibrosis were markedly reduced by the depletion of pDCs or blockade of type I IFN signaling; moreover, such treatment was accompanied by a marked reduction of pancreatic expression of IL-33...
April 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28371335/genetic-susceptibility-to-severe-asthma-with-fungal-sensitization
#14
N L Overton, A Simpson, P Bowyer, D W Denning
Severe asthma is problematic and its pathogenesis poorly understood. Fungal sensitization is common, and many patients with severe asthma with fungal sensitization (SAFS), used to denote this subgroup of asthma, respond to antifungal therapy. We have investigated 325 haplotype-tagging SNPs in 22 candidate genes previously associated with aspergillosis in patients with SAFS, with comparisons in atopic asthmatics and healthy control patients, of whom 47 SAFS, 279 healthy and 152 atopic asthmatic subjects were genotyped successfully...
March 31, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28370295/hypoxia-mediates-mitochondrial-biogenesis-in-hepatocellular-carcinoma-to-promote-tumor-growth-via-hmgb1-and-tlr9-interaction
#15
Samer Tohme, Hamza O Yazdani, Yao Liu, Patricia Loughran, Dirk J van der Windt, Hai Huang, Richard L Simmons, Sruti Shiva, Sheng Tai, Allan Tsung
The ability of cancer cells to survive and grow under hypoxic conditions has been known for decades, but the mechanisms remain poorly understood. Under certain conditions, cancer cells undergo changes in their bioenergetic profile to favor mitochondrial respiration by activating the peroxisome proliferator-activated receptor gamma (PGC-1α) and upregulating mitochondrial biogenesis. In this study, we hypothesized that augmented mitochondrial biogenesis plays a critical role for cancer cells to survive hypoxia...
March 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28365257/corrigendum-to-epicutaneous-immunization-with-phosphorylcholine-conjugated-to-bovine-serum-albumin-pc-bsa-and-tlr9-ligand-cpg-alleviates-pneumococcal-pneumonia-in-mice-pharmacol-rep-66-2014-570-575
#16
Monika Majewska-Szczepanik, Natsuo Yamamoto, Philip W Askenase, Marian Szczepanik
No abstract text is available yet for this article.
March 29, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28363843/toll-like-receptor-9-mediates-paraquat-induced-acute-lung-injury-an-in-vitro-and-in-vivo-study
#17
Haitao Shen, Na Wu, Yu Wang, Lichun Zhang, Xiao Hu, Zhiguang Chen, Min Zhao
AIMS: This study aimed to investigate the role of Toll-like receptor 9 in paraquat-induced acute lung injury (ALI). MAIN METHODS: For in vivo study,C57BL mice were randomly assigned into the vehicle control group, paraquat group, paraquat + antagonist (ODN2088) group, and antagonist (ODN2088) group (n=24 per group). After paraquat 30mg/kg ip for 2, 24 and 48h, serum samples and lung tissues were collected to evaluate ALI and TLR9 signaling. As for in vitro research A549 cells were randomly divided into the control group, paraquat group, paraquat + TLR9 siRNA group, and TLR9 siRNA group...
March 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/28360906/efficacy-of-resistance-to-francisella-imparted-by-ity-nramp-slc11a1-depends-on-route-of-infection
#18
Daniel A Powell, Jeffrey A Frelinger
Natural resistance-associated macrophage protein (NRAMP) encoded by the Slc11a1 gene is a membrane-associated transporter of divalent metal ions. Murine Slc11a1 has two known alleles, a functional Slc11a1(Gly169), which is found in DBA2/J, NOD/LtJ, and 129p3/J and related mouse strains, and a non-functional Slc11a1(Asp169), that is found in C56Bl/6J (B6) and BALB/cJ mice. B6 mice congenic for Slc11a1(Gly169) (B6-Slc11a1(G169) ) are markedly resistant to the intracellular pathogens Salmonella, Leishmania, and Mycobacterium tuberculosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28359672/cloning-and-expression-analysis-of-a-toll-like-receptor-21-tlr21-gene-from-turbot-scophthalmus-maximus
#19
Song Li, Guanjie Wang, Dahai Liu, Qiuming Liu, Guobin Hu
Toll-like receptor 21 (TLR21) is a non-mammalian TLR recognizing unmethylated CpG DNA and considered as a functional homolog of mammalian TLR9. In the present study, a TLR21 gene was cloned from turbot, Scophthalmus maximus, its immune responsive expression was subsequently studied in vivo. The turbot (Sm)TLR21 gene is an intronless gene with a length of 3527 bp and encodes a peptide of 984 amino acids. The deduced protein possesses a signal peptide sequence, a leucine-rich repeat (LRR) domain composed of 16 LRR motifs, a transmembrane (TM) region and a Toll/interleukin-1 receptor (TIR) domain...
March 27, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28356656/cpg-type-a-induction-of-an-early-protective-environment-in-experimental-multiple-sclerosis
#20
James Crooks, Marco Gargaro, Carmine Vacca, Claudia Volpi, Matteo Pirro, Giulia Scalisi, Antonella Turco, Rita Romani, Davide Matino, Abdolmohamad Rostami, Paolo Puccetti, Bruno Gran, Francesca Fallarino
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS), and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4(+) T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs), typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs)...
2017: Mediators of Inflammation
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