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https://www.readbyqxmd.com/read/28698123/identification-molecular-evolution-of-toll-like-receptors-in-a-tibetan-schizothoracine-fish-gymnocypris-eckloni-and-their-expression-profiles-in-response-to-acute-hypoxia
#1
Delin Qi, Mingzhe Xia, Yan Chao, Yongli Zhao, Rongrong Wu
Hypoxia plays an important role in regulating a variety of physiological responses as well as in pathological situations, but to date the roles of Toll-like receptors (TLRs) in fish in response to hypoxia are still poorly understood. Here, we sequenced the transcriptome of G. eckloni and identified the members of TLR family by scanning transcriptome, and then investigated the expression profiles of a complete set of TLRs in G. eckloni in response to acute hypoxia (4 h at DO = 0.3 ± 0.1 mg/L). The de novo-assembled transcriptome consisted of a total of 162,235 transcripts, further clustered into 110,231 unigenes...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28671847/identification-and-optimization-of-pyrrolo-3-2-d-pyrimidine-toll-like-receptor-7-tlr7-selective-agonists-for-the-treatment-of-hepatitis-b
#2
David Craig McGowan, Florence Herschke, Frederik Pauwels, Bart Stoops, Ilham Smyej, Stefaan Last, Serge Pieters, Werner Embrechts, Mourad Daoubi Khamlichi, Tine Thoné, Bertrand Van Schoubroeck, Wendy Mostmans, Debbie Wuyts, Dorien Verstappen, Annick Scholliers, Dorien De Pooter, Deborah Dhuyvetter, Herman Borghys, Marianne Tuefferd, Eric Arnoult, Jin Hong, Gregory Fanning, Jacques Bollekens, Vijay Urmaliya, Ard Teisman, Helen Horton, Tim H M Jonckers, Pierre Jean Marie Bernard Raboisson
Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 activity, which may be detrimental to the tolerability of the candidate drug. Oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (ISG) response in mice and cynomolgus monkeys. We aimed for a high first pass effect, limiting cytokine induction systemically, and demonstrated the potential for the immunotherapy of viral hepatitis...
July 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28656222/activation-of-the-toll-like-receptor-8-pathway-increases-the-immunogenicity-of-mesenchymal-stem-cells-from-umbilical-cord
#3
Yu Yang, Yanwen Wang, Li Li, Fei Chen, Peng Zhang
Mesenchymal stem cells (MSCs) are now widely used in clinical cell‑based therapy due to their characteristics of low immunogenicity, multiple differentiation potency and the capability to modulate immune responses. However, accumulated research has indicated the absence of engrafted MSCs because of the increased immunogenicity of MSCs. Toll‑like receptors (TLRs) are essential for the innate immune response and regulating the biological function of MSCs. The present study used human umbilical cord‑derived MSCs (UCMSCs) and activated the TLR8 pathway of UCMSCs to study the role of TLR8 in mediating the immune status of UCMSCs...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28648870/tlr7-and-tlr8-agonist-resiquimod-r848-differently-regulates-mif-expression-in-cells-and-organs
#4
Yao Mawulikplimi Adzavon, Pengxiang Zhao, Baobei Lv, Mengyu Liu, Xin Zhang, Fei Xie, Linqi Yang, Lei Shang, Mingzi Zhang, Qinjian Li, Xuemei Ma
Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28639412/the-role-of-microrna-5196-in-the-pathogenesis-of-systemic-sclerosis
#5
Marzena Ciechomska, Patryk Zarecki, Michal Merdas, Jerzy Swierkot, Ewa Morgiel, Piotr Wiland, Wlodzimierz Maslinski, Katarzyna Bogunia-Kubik
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by tissue fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from patients with SSc play an important role in early stages of SSc pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), IL-8 and reactive oxygen species (ROS) induction. However, the exact factors that contribute to chronic inflammation and subsequently fibrosis progression are still unknown...
June 21, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28626766/involvement-of-the-toll-like-receptor-nitric-oxide-signaling-pathway-in-the-pathogenesis-of-cervical-cancer-caused-by-high-risk-human-papillomavirus-infection
#6
Jie Li, Heping Rao, Chang'e Jin, Jinrong Liu
Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28592890/polymorphism-in-the-gene-encoding-toll-like-receptor-10-may-be-associated-with-asthma-after-bronchiolitis
#7
Sari Törmänen, Matti Korppi, Johanna Teräsjärvi, Juho Vuononvirta, Petri Koponen, Merja Helminen, Qiushui He, Kirsi Nuolivirta
Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.4 years (mean) in 135 children hospitalised for bronchiolitis in infancy. The outcome measure was current or previous asthma. Current asthma was more common (30%) in children with the variant AG or GG genotype in the TLR10 rs4129009 gene versus those who were homozygous for the major allele A (11%) (p = 0...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28582454/insights-on-the-mechanism-of-action-of-immunostimulants-in-relation-to-their-pharmacological-potency-the-effects-of-imidazoquinolines-on-tlr8
#8
Carlos Kubli-Garfias, Ricardo Vázquez-Ramírez, Cynthia Trejo-Muñoz, Arturo Berber
Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1...
2017: PloS One
https://www.readbyqxmd.com/read/28576825/identification-of-an-optimized-2-o-methylated-tri-nucleotide-rna-motif-inhibiting-toll-like-receptor-7-and-8
#9
Felix C F Schmitt, Isabel Freund, Markus A Weigand, Mark Helm, Alexander H Dalpke, Tatjana Eigenbrod
Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic as compared to eukaryotic RNA allow innate immune cells to discriminate between 'host' and 'foreign' RNA. Ribose 2'-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2'-O-methylation has to occur to mediate its inhibitory activity remains largely undefined...
June 2, 2017: RNA
https://www.readbyqxmd.com/read/28571545/potential-medications-or-compounds-acting-on-toll-like-receptors-in-cerebral-ischemia
#10
Man Li, Jing Liu, Ying Bi, Jixiang Chen, Lei Zhao
Toll-like receptors (TLRs) have been suggested to play an integral role in the process of inflammatory response after ischemic injury. Amongst all 9 TLRs present in the brain, functions of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 have been studied in recent years. The MyD88 pathway and TIR domain-containing adaptor inducing interferon pathway are involved in these pathophysiological changes. For its important role, the therapeutic potential of strategies acting on TLRs needs further evaluation. Feasible approaches may function in the following respects, such as methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the preconditioning or post conditioning with TLR ligands or minor cerebral ischemia...
June 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28565836/the-immune-mechanism-of-intestinal-tract-toll-like-receptor-in-mediating-ev71-virus-type-severe-hand-foot-and-mouth-disease-and-the-mapk-pathway
#11
Lei Zhu, Weihua Li, Gongjian Qi, Na Liu, Liping Sheng, Lei Shang, Boxiang Qi
Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)-infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28551415/interferon-%C3%AE-response-is-impaired-by-hepatitis-b-virus-infection-in-tupaia-belangeri
#12
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Haiying Chi, Takahiro Sanada, Naoki Yamamoto, Bouchra Kitab, Takumi Haraguchi, Rika Matsuyama, Chimène Nze Nkogue, Hitoshi Hatai, Noriaki Miyoshi, Shuko Murakami, Yasuhito Tanaka, Jun-Ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Michinori Kohara, Kyoko Tsukiyama-Kohara
To date, the chimpanzee has been used as the natural infection model for hepatitis B virus (HBV). However, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (Tupaia belangeri) as a new model for HBV infection and characterized its intrahepatic innate immune response upon HBV infection. First, we compared the propagation of HBV genotypes A2 and C in vivo in tupaia hepatocytes. At 8-10days post infection (dpi), the level of HBV-A2 propagation in the tupaia liver was found to be higher than that of HBV-C...
May 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28544689/class-ii-obese-and-healthy-pregnant-controls-exhibit-indistinguishable-pro-and-anti-inflammatory-immune-responses-to-caesarian-section
#13
Caroline Graham, Mullein Thorleifson, William P Stefura, Duane J Funk, Kent T HayGlass
INTRODUCTION: Obesity during pregnancy is associated with meta-inflammation and an increased likelihood of clinical complications. Surgery results in intense, acute inflammatory responses in any individual. Because obese individuals exhibit constitutive inflammatory responses and high rates of Caesarian section, it is important to understand the impact of surgery in such populations. Whether more pronounced pro-inflammatory cytokine responses and/or counterbalancing changes in anti-inflammatory immune modulators occurs is unknown...
May 25, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28530246/short-single-stranded-dna-degradation-products-augment-the-activation-of-toll-like-receptor-9
#14
Jelka Pohar, Duško Lainšček, Karolina Ivičak-Kocjan, Miša-Mojca Cajnko, Roman Jerala, Mojca Benčina
Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28500073/fc%C3%AE-riiia-signaling-modulates-endosomal-tlr-responses-in-human-cd4-t-cells
#15
Anil K Chauhan
Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs and deliver them to endosomes, where they are recognized by nucleic acid-sensing TLRs (NA-TLRs). We show that in CD4(+) T cells, NA-TLRs, TLR3, TLR8, and TLR9 are upregulated by FcγRIIIa-pSyk cosignaling and localize with FcγRIIIa on the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in discriminating self versus viral nucleic acid...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28495399/evaluation-of-toll-like-receptor-gene-family-variants-as-prognostic-biomarkers-in-rheumatoid-arthritis
#16
Silvia Torices, Lorena Alvarez-Rodríguez, Ignacio Varela, Pedro Muñoz, Alejandro Balsa, M López-Hoyos, Víctor Martinez-Taboada, Jose L Fernández-Luna
Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in the activation of innate and adaptive immune responses, and influence the activity of NFκB, a key player in chronic inflammation. We aimed at investigating the association of TLR allelic variants with susceptibility and severity of RA through a systematic, high-throughput, analysis of TLR genes. All coding exons and flanking regions of nine members of the TLR family (TLR1-9) were analyzed in 66 patients with RA and 30 healthy controls by next generation sequencing...
May 7, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28472897/the-anticancer-effect-of-mebendazole-may-be-due-to-m1-monocyte-macrophage-activation-via-erk1-2-and-tlr8-dependent-inflammasome-activation
#17
Kristin Blom, Wojciech Senkowski, Malin Jarvius, Malin Berglund, Jenny Rubin, Lena Lenhammar, Vendela Parrow, Claes Andersson, Angelica Loskog, Mårten Fryknäs, Peter Nygren, Rolf Larsson
Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation...
May 4, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#18
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28403045/polymorphisms-of-mannose-binding-lectin-and-toll-like-receptors-2-3-4-7-and-8-and-the-risk-of-respiratory-infections-and-acute-otitis-media-in-children
#19
Laura Toivonen, Juho Vuononvirta, Jussi Mertsola, Matti Waris, Qiushui He, Ville Peltola
BACKGROUND: Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media. METHODS: In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28392469/susceptibility-and-initial-immune-response-of-tupaia-belangeri-cells-to-dengue-virus-infection
#20
Mohammad Enamul Hoque Kayesh, Bouchra Kitab, Takahiro Sanada, Daisuke Hayasaka, Kouichi Morita, Michinori Kohara, Kyoko Tsukiyama-Kohara
Dengue is an emerging disease of great public health significance worldwide. The lack of a suitable infection model has hampered dengue virus (DENV) pathogenesis study, and developing a suitable small animal model has been a long-standing challenge. The aim of this study was to develop a feasible experimental model of DENV infection using Tupaia belangeri. The susceptibility of tupaia to DENV infection and characteristics of its innate immune response were examined in vitro. We found that tupaia fibroblast cells support replication of DENV serotypes 1-4 with a linear increase in viral load 24-96h post-infection in both cells and culture supernatants...
April 6, 2017: Infection, Genetics and Evolution
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