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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
#1
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/28620298/anti-tumor-activity-of-toll-like-receptor-7-agonists
#2
REVIEW
Huju Chi, Chunman Li, Flora Sha Zhao, Li Zhang, Tzi Bun Ng, Guangyi Jin, Ou Sha
Toll-like receptors (TLRs) are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28619954/a-novel-immune-biomarker-ifi27-discriminates-between-influenza-and-bacteria-in-patients-with-suspected-respiratory-infection
#3
Benjamin M Tang, Maryam Shojaei, Grant P Parnell, Stephen Huang, Marek Nalos, Sally Teoh, Kate O'Connor, Stephen Schibeci, Amy L Phu, Anand Kumar, John Ho, Adrienne F A Meyers, Yoav Keynan, Terry Ball, Amarnath Pisipati, Aseem Kumar, Elizabeth Moore, Damon Eisen, Kevin Lai, Mark Gillett, Robert Geffers, Hao Luo, Fahad Gul, Jens Schreiber, Sandra Riedel, David Booth, Anthony McLean, Klaus Schughart
Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers...
June 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28615284/tcl1a-snps-and-estrogen-mediated-toll-like-receptor-myd88-dependent-nf-%C3%AE%C2%BAb-activation-snp-and-serm-dependent-modification-of-inflammation-and-immune-response
#4
Ming-Fen Ho, James N Ingle, Tim Bongartz, Krishna R Kalari, Paul E Goss, Lois E Shepherd, Taisei Mushiroda, Michiaki Kubo, Liewei Wang, Richard M Weinshilboum
In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy of breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the TCL1A gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol (E2), but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, TCL1A genotype influenced the "downstream" expression of a series of cytokines and chemokines and had a striking effect on NF-κB transcriptional activity...
June 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28606989/tlr7-8-activation-in-neutrophils-impairs-immune-complex-phagocytosis-through-shedding-of-fcgriia
#5
Christian Lood, Sabine Arve, Jeffrey Ledbetter, Keith B Elkon
Neutrophils play a crucial role in host defense. However, neutrophil activation is also linked to autoimmune diseases such as systemic lupus erythematosus (SLE), where nucleic acid-containing immune complexes (IC) drive inflammation. The role of Toll-like receptor (TLR) signaling in processing of SLE ICs and downstream inflammatory neutrophil effector functions is not known. We observed that TLR7/8 activation leads to a furin-dependent proteolytic cleavage of the N-terminal part of FcgRIIA, shifting neutrophils away from phagocytosis of ICs toward the programmed form of necrosis, NETosis...
June 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28601925/enhanced-stimulation-of-human-tumor-specific-t-cells-by-dendritic-cells-matured-in-the-presence-of-interferon-%C3%AE-and-multiple-toll-like-receptor-agonists
#6
Tanja Lövgren, Dhifaf Sarhan, Iva Truxová, Bhavesh Choudhary, Roeltje Maas, Jeroen Melief, Maria Nyström, Ulrika Edbäck, Renee Vermeij, Gina Scurti, Michael Nishimura, Giuseppe Masucci, Alex Karlsson-Parra, Andreas Lundqvist, Lars Adamson, Rolf Kiessling
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28601846/nadph-oxidase-depletion-in-neutrophils-from-patients-with-cirrhosis-and-restoration-via-toll-like-receptor-7-8-activation
#7
Loïc Rolas, Abdelali Boussif, Emmanuel Weiss, Philippe Lettéron, Oualid Haddad, Jamel El-Benna, Pierre-Emmanuel Rautou, Richard Moreau, Axel Périanin
OBJECTIVE: Cirrhosis downregulates phagocyte oxidant production via their antibacterial superoxide-generating system, NADPH oxidase (NOX2) and increases patients' susceptibility to infection and mortality rate. To explore novel biochemical parameters that explain susceptibility to infections, we investigated the expression of NOX2 and partners in neutrophils of patients with severe alcoholic cirrhosis and have provided a novel approach to restore superoxide production capacity in patients' neutrophils and blood...
June 10, 2017: Gut
https://www.readbyqxmd.com/read/28601430/imiquimod-induced-autophagy-is-regulated-by-er-stress-mediated-pkr-activation-in-cancer-cells
#8
Shu-Hao Chang, Shi-Wei Huang, Sin-Ting Wang, Kai-Cheng Chung, Chia-Wei Hsieh, Jun-Kai Kao, Yi-Ju Chen, Chun-Ying Wu, Jeng-Jer Shieh
BACKGROUND: Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo...
May 2, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28600543/innate-and-adaptive-immunity-are-progressively-activated-in-parallel-with-renal-injury-in-the-5-6-renal-ablation-model
#9
Camilla Fanelli, Simone C A Arias, Flavia G Machado, Jessica K Okuma, Denise M A C Malheiros, Hatylas Azevedo, Carlos A Moreira-Filho, Niels O S Camara, Clarice K Fujihara, Roberto Zatz
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1β and NLRP3 were individually assessed...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595240/toll-like-receptor-7-is-overexpressed-in-the-bladder-of-hunner-type-interstitial-cystitis-and-its-activation-in-the-mouse-bladder-can-induce-cystitis-and-bladder-pain
#10
Koji Ichihara, Naoki Aizawa, Yoshiyuki Akiyama, Jun Kamei, Naoya Masumori, Karl-Erik Andersson, Yukio Homma, Yasuhiko Igawa
Toll-like receptor 7 (TLR7) is associated with the pathophysiology of systemic lupus erythematosus and Sjögren syndrome, well-known diseases accompanying interstitial cystitis (IC). We studied TLR7 expression in the bladder of patients with Hunner-type IC (HIC) and its functional roles in bladder inflammation and nociception using mice. Bladder biopsy specimens were obtained from patients with HIC. Specimens from the noncancerous portion of the bladder of patients with bladder cancer served as controls. The specimens were examined by immunohistochemistry and real-time polymerase chain reaction of TLR7...
May 6, 2017: Pain
https://www.readbyqxmd.com/read/28592890/polymorphism-in-the-gene-encoding-toll-like-receptor-10-may-be-associated-with-asthma-after-bronchiolitis
#11
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/28592561/vaccine-priming-is-restricted-to-draining-lymph-nodes-and-controlled-by-adjuvant-mediated-antigen-uptake
#12
Frank Liang, Gustaf Lindgren, Kerrie J Sandgren, Elizabeth A Thompson, Joseph R Francica, Anja Seubert, Ennio De Gregorio, Susan Barnett, Derek T O'Hagan, Nancy J Sullivan, Richard A Koup, Robert A Seder, Karin Loré
The innate immune mechanisms by which adjuvants enhance the potency and protection of vaccine-induced adaptive immunity are largely unknown. We introduce a model to delineate the steps of how adjuvant-driven innate immune activation leads to priming of vaccine responses using rhesus macaques. Fluorescently labeled HIV-1 envelope glycoprotein (Env) was administered together with the conventional aluminum salt (alum) adjuvant. This was compared to Env given with alum with preabsorbed Toll-like receptor 7 (TLR7) ligand (alum-TLR7) or the emulsion MF59 because they show superiority over alum for qualitatively and quantitatively improved vaccine responses...
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28591543/influence-of-polyphenol-rich-diet-on-exercise-induced-immunomodulation-in-male-endurance-athletes
#13
Korbinian Lackermair, Johannes Scherr, Georg Waidhauser, Heiko Methe, Eva Hoster, David C Nieman, Alan Hanley, Sebastian Clauss, Martin Halle, Thomas Nickel
<u>Introduction:</u> Stress is associated with increased susceptibility to infection. We investigated if the mechanism involves immunomodulation of dendritic cells and whether this can be inhibited by a polyphenol-rich diet. <u>Methods:</u> Blood samples were taken from a total of 100 male endurance athletes at five time points around a marathon run: four weeks before, during one week before, and immediately, 24hours and 72hours after. Participants were randomized into two double blinded groups...
June 7, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28588009/exosome-derived-mir-25-3p-and-mir-92a-3p-stimulate-liposarcoma-progression
#14
Lucia Casadei, Federica Calore, Chad J Creighton, Michele Guescini, Kara Batte, O Hans Iwenofu, Abeba Zewdu, Danielle Braggio, Kate Lynn Bill, Paolo Fadda, Francesca Lovat, Gonzalo Lopez, Pierluigi Gasparini, James L Chen, Raleigh D Kladney, Gustavo Leone, Dina Lev, Carlo M Croce, Raphael E Pollock
Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease...
June 6, 2017: Cancer Research
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
#15
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/28580131/recent-insights-into-the-implications-of-metabolism-in-plasmacytoid-dendritic-cell-innate-functions-potential-ways-to-control-these-functions
#16
REVIEW
Philippe Saas, Alexis Varin, Sylvain Perruche, Adam Ceroi
There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β)...
2017: F1000Research
https://www.readbyqxmd.com/read/28578407/rnai-screen-and-proteomics-reveal-nxf1-as-a-novel-regulator-of-irf5-signaling
#17
Bishi Fu, Mengmeng Zhao, Lingyan Wang, Girish Patil, Jennifer A Smith, Ignacio J Juncadella, Ljiljana Zuvela-Jelaska, Martin E Dorf, Shitao Li
Interferon regulatory factor 5 (IRF5) is a key transcription factor of innate immunity, which plays an important role in host restriction to viral infection and inflammation. Genome-wide association studies have implied the association of IRF5 with several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren's syndrome, inflammatory bowel disease and multiple sclerosis. However, the regulation of IRF5-mediated immunity is not well understood. To uncover new regulators in IRF5 pathway, we used two "omics" approaches: affinity purification coupled with mass spectrometry and a high throughput RNAi screen...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28576825/identification-of-an-optimized-2-o-methylated-tri-nucleotide-rna-motif-inhibiting-toll-like-receptor-7-and-8
#18
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/28572564/plasmacytoid-dendritic-cells-appear-inactive-during-sub-microscopic-plasmodium-falciparum-blood-stage-infection-yet-retain-their-ability-to-respond-to-tlr-stimulation
#19
Jessica R Loughland, Gabriela Minigo, Derek S Sarovich, Matt Field, Peta E Tipping, Marcela Montes de Oca, Kim A Piera, Fiona H Amante, Bridget E Barber, Matthew J Grigg, Timothy William, Michael F Good, Denise L Doolan, Christian R Engwerda, Nicholas M Anstey, James S McCarthy, Tonia Woodberry
Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28571545/potential-medications-or-compounds-acting-on-toll-like-receptors-in-cerebral-ischemia
#20
Man Li, Jing Liu, Ying Bi, Jixiang Chen, Lei Zhao
Toll-like receptors have been suggested to play an integral role in the process of inflammatory response after ischemic injury. Of all 9 TLRs presenting in 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. Since the important role, the therapeutic potential of strategies acting on TLRs should be evaluated. Feasible approaches may function in the following respects, methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the preconditioning or postconditioning with TLR ligands or minor cerebral ischemia...
June 1, 2017: Current Neuropharmacology
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