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Toll-like Receptors

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https://www.readbyqxmd.com/read/28535426/new-role-of-pcsk9-in-atherosclerotic-inflammation-promotion-involving-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#1
Zhi-Han Tang, Juan Peng, Zhong Ren, Jing Yang, Ting-Ting Li, Tao-Hua Li, Zuo Wang, Dang-Heng Wei, Lu-Shan Liu, Xi-Long Zheng, Zhi-Sheng Jiang
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression...
April 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28533893/expression-of-pattern-recognition-receptor-genes-and-mortality-in-patients-with-colorectal-adenocarcinoma
#2
Kathryn E Royse, Liang Chen, David H Berger, Michael M Ittmann, Hashem B El-Serag, Courtney J Balentine, David Y Graham, Peter A Richardson, Rolando E Rumbaut, Xiaoyun Shen, Donna L White, Li Jiao
Toll-like receptors (TLRs) and the receptor for advanced glycation end products (AGER) are pattern recognition receptors that regulate intestinal inflammatory homeostasis. However, their relevance in colorectal cancer (CRC) prognosis is unclear. We investigated expression of TLRs, AGER, and interacting proteins in association with CRC mortality in a retrospective cohort study of 65 males diagnosed with primary resectable CRC between 2002 and 2009. Multiplex quantitative nuclease protection assay was used to quantify the expression of 19 genes in archived tissues of tumor and paired adjacent normal mucosa...
2017: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/28533483/high-il-1r8-expression-in-breast-tumors-promotes-tumor-growth-and-contributes-to-impaired-antitumor-immunity
#3
Luis Felipe Campesato, Ana Paula M Silva, Luna Cordeiro, Bruna R Correa, Fabio C P Navarro, Rafael F Zanin, Marina Marçola, Lilian T Inoue, Mariana L Duarte, Martina Molgora, Fabio Pasqualini, Matteo Massara, Pedro Galante, Romualdo Barroso-Sousa, Nadia Polentarutti, Federica Riva, Erico T Costa, Alberto Mantovani, Cecilia Garlanda, Anamaria A Camargo
Tumors develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. The identification of mechanisms leading to local immune dysregulation is critical to improve cancer therapy. We here demonstrate that Interleukin-1 receptor 8 (IL-1R8 - previously known as SIGIRR/TIR8), a negative regulator of Toll-Like and Interleukin-1 Receptor family signaling, is up-regulated during breast epithelial cell transformation and in primary breast tumors. IL-1R8 expression in transformed breast epithelial cells reduced IL-1-dependent NF-κB activation and production of pro-inflammatory cytokines, inhibited NK cell activation and favored M2-like macrophage polarization...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533225/multi-functional-effects-of-a-small-molecule-stat3-inhibitor-on-nash-and-hcc-in-mice
#4
Kwang Hwa Jung, Wonbeak Yoo, Heather L Stevenson, Dipti Deshpande, Hong Shen, Mihai Gagea, Suk-Young Yoo, Jing Wang, Thomas Kris Eckols, Uddalak Bharadwaj, David J Tweardy, Laura Beretta
The incidence of hepatocellular carcinoma (HCC) is increasing in the United States and liver cancer is the second leading cause of cancer-related mortality worldwide. Non-alcoholic steatohepatitis (NASH) is becoming an important risk for HCC and most patients with HCC have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat HCC in the context of NASH and cirrhosis are urgently needed. <br /><br />Experimental Design: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in HCC tumors...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28533056/white-matter-damage-after-traumatic-brain-injury-a-role-for-damage-associated-molecular-patterns
#5
REVIEW
Molly Braun, Kumar Vaibhav, Nancy M Saad, Sumbul Fatima, John R Vender, Babak Baban, Md Nasrul Hoda, Krishnan M Dhandapani
Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI...
May 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28532825/growth-performance-reproductive-traits-and-offspring-survivability-of-genetically-modified-rams-overexpressing-toll-like-receptor-4
#6
Yu-Chang Yao, Hong-Bing Han, Xu-Ting Song, Shou-Long Deng, Yu-Feng Liu, Ming-Hai Lu, Yun-Hai Zhang, Mei-Yu Qi, Hai-Juan He, Su-Mei Wang, Guo-Shi Liu, Wu Li, Zheng-Xing Lian
Genetic modification provides a means to enhancing disease resistance in animals. Toll-like receptor 4 (TLR4), a member of the TLR family, is critical for the recognition of lipopolysaccharide (LPS)/endotoxin from Gram-negative bacteria by host immune cells, which initiates cell activation and subsequently triggers a proinflammatory response to the invading pathogens. In this study, the first generation of genetically modified (GM) sheep overexpressing TLR4 was produced by microinjection for better disease resistance...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28531216/impact-of-mutations-in-toll-like-receptor-pathway-genes-on-esophageal-carcinogenesis
#7
Daffolyn Rachael Fels Elliott, Juliane Perner, Xiaodun Li, Martyn F Symmons, Brett Verstak, Matthew Eldridge, Lawrence Bower, Maria O'Donovan, Nick J Gay, Rebecca C Fitzgerald
Esophageal adenocarcinoma (EAC) develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting the Toll-like receptor (TLR) pathway could disrupt innate immune signaling and promote a microenvironment that favors tumorigenesis. Through interrogating whole genome sequencing data from 171 EAC patients, we showed that non-synonymous mutations collectively affect the TLR pathway in 25/171 (14...
May 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28531130/comparative-safety-and-efficacy-profile-of-a-novel-oil-in-water-vaccine-adjuvant-comprising-vitamins-a-and-e-and-a-catechin-in-protective-anti-influenza-immunity
#8
Sapna Patel, Yasser Faraj, Debra K Duso, William W Reiley, Erik A Karlsson, Stacey Schultz-Cherry, Michael Vajdy
Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA) mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS), based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus...
May 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28530841/the-increased-expression-of-toll-like-receptor-4-in-renal-and-skin-lesions-in-lupus-erythematosus
#9
Nesrine Elloumi, Raouia Fakhfakh, Lobna Ayadi, Khadija Sellami, Olfa Abida, Mariem Ben Jmaa, Tahya Sellami, Khawla Kammoun, Hatem Masmoudi
Toll-like receptor 4 (TLR-4), a bacterial lipopolysaccharide sensor, is an innate immunity essential modulator. It is expressed on both immune and non-immune cells and may contribute to the cutaneous and renal manifestations during lupus erythematosus (LE). Our purpose is to evaluate TLR-4 expression and analyzing its role in lupus nephritis (LN) and chronic cutaneous lupus erythematosus (CLE) pathogenesis. TLR-4 immunohistochemical staining was performed on 30 LN renal biopsies compared with 11 healthy renal tissues and 30 skin biopsies from CLE patients compared with 15 normal individuals...
May 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28530548/critical-role-of-rig-i-and-mda5-in-early-and-late-stages-of-tulane-virus-infection
#10
Preeti Chhabra, Priya Ranjan, Theresa Cromeans, Suryaprakash Sambhara, Jan Vinjé
Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)...
May 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28530246/short-single-stranded-dna-degradation-products-augment-the-activation-of-toll-like-receptor-9
#11
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/28530169/commensal-derived-omvs-elicit-a-mild-proinflammatory-response-in-intestinal-epithelial-cells
#12
Daniel A Patten, Enas Hussein, Scott P Davies, Paul N Humphreys, Andrew Collett
Under normal physiological conditions, the intestinal immunity remains largely hyporesponsive to the commensal microbiota, yet also retains the inherent ability to rapidly respond to pathogenic antigens. However, immunomodulatory activities of extracellular products from commensal bacteria have been little studied, with previous investigations generally utilizing the live bacterium to study microbiota-epithelial interactions. In this study, we demonstrate that extracellular products of a commensal bacterium, Escherichia coli C25, elicit a moderate release of proinflammatory IL-8 and stimulate transcriptional up-regulation of Toll-like receptors (TLRs) in intestinal epithelial cell lines HT29-19A and Caco-2...
May 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28529955/identification-of-transcriptional-modules-and-key-genes-in-chickens-infected-with-salmonella-enterica-serovar-pullorum-using-integrated-coexpression-analyses
#13
Bao-Hong Liu, Jian-Ping Cai
Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA) and differential coexpression analysis (DCEA) to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529452/estradiol-suppresses-tlr4-triggered-apoptosis-of-decidual-stromal-cells-and-drives-an-anti-inflammatory-th2-shift-by-activating-sgk1
#14
Yiyun Lou, Minhao Hu, Qijing Wang, Mu Yuan, Ning Wang, Fang Le, Lejun Li, Shisi Huang, Liya Wang, Xiangrong Xu, Fan Jin
A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28528860/purifying-selection-and-concerted-evolution-of-rna-sensing-toll-like-receptors-in-migratory-waders
#15
Nynke Raven, Simeon Lisovski, Marcel Klaassen, Nathan Lo, Thomas Madsen, Simon Y W Ho, Beata Ujvari
Migratory birds encounter a broad range of pathogens during their journeys, making them ideal models for studying immune gene evolution. Despite the potential value of these species to immunoecology and disease epidemiology, previous studies have typically focused on their adaptive immune gene repertoires. In this study, we examined the evolution of innate immune genes in three long-distance migratory waders (order Charadriiformes). We analysed two parts of the extracellular domains of two Toll-like receptors (TLR3 and TLR7) involved in virus recognition in the Sanderling (Calidris alba), Red-necked Stint (Calidris ruficollis), and Ruddy Turnstone (Arenaria interpres)...
May 18, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28528507/mertk-does-not-mediate-phagocytosis-of-staphylococcus-aureus-but-attenuates-inflammation-induced-by-staphylococcal-lipoteichoic-acid-through-blocking-nf-%C3%AE%C2%BAb-activation
#16
Bing Zhang, Huimei Wu, Lei Fang, Peishan Ding, Ke Xu, Qingbin Yang, Rongyu Liu
Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis...
May 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527686/local-innate-responses-and-protective-immunity-after-intradermal-immunization-with-bovine-viral-diarrhea-virus-e2-protein-formulated-with-a-combination-adjuvant-in-cattle
#18
Sams M A Sadat, Marlene Snider, Ravendra Garg, Robert Brownlie, Sylvia van Drunen Littel-van den Hurk
Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens in cattle. Recently, we developed a novel adjuvant platform (TriAdj) that includes a toll-like receptor 3 agonist, poly (I:C); an innate defense regulatory peptide; and water-soluble polymer, poly[di(sodiumcarboxylatoethylphenoxy)]-phosphazene (PCEP). To develop a needle-free intradermal (ID) subunit vaccine, the BVDV type-2 E2 protein was formulated with TriAdj, and immune protection was evaluated in calves against a BVDV-2 strain. Intradermal delivery of E2/TriAdj elicited robust virus neutralizing antibodies and cell-mediated immune responses including CD4(+) and CD8(+) T-cell responses...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28526573/transcriptomic-variation-of-locally-infected-skin-of-epinephelus-coioides-reveals-the-mucosal-immune-mechanism-against-cryptocaryon-irritans
#19
Yazhou Hu, Anxing Li, Yang Xu, Biao Jiang, Geling Lu, Xiaochun Luo
Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28525945/the-protective-effect-of-luteolin-on-myocardial-ischemia-reperfusion-i-r-injury-through-tlr4-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-pathway
#20
Xu Zhang, Qianming Du, Yan Yang, Jianing Wang, Shuai Dou, Chao Liu, Junguo Duan
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM)...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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