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https://www.readbyqxmd.com/read/29786555/innate-immunity-in-stem-cell-derived-hepatocytes
#1
REVIEW
Lena Fischer, David C Hay, Cliona O'Farrelly
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784900/irak-inhibitor-protects-the-intestinal-tract-of-necrotizing-enterocolitis-by-inhibiting-the-toll-like-receptor-tlr-inflammatory-signaling-pathway-in-rats
#2
Yu Hou, Xin Lu, Yueju Zhang
BACKGROUND The aim of this study was to assess the effects of interleukin-1 (IL-1) receptor associated kinase (IRAK) inhibitors on intestinal injury induced by necrotizing enterocolitis (NEC) in neonatal rats and its regulation on the intestinal Toll-like receptor (TLR) inflammatory signaling pathway. MATERIAL AND METHODS The neonatal rat models of NEC were established though hypoxia-cold stimulation. All rats were divided into 3 groups: an NEC model group (NEC group), an IRAK inhibitor group (IRAKI group), and a normal control group (NC group)...
May 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29784886/-legionella-pneumophila-is-directly-sensitive-to-2-deoxyglucose-phosphate-via-its-uhpc-transporter-but-is-indifferent-to-shifts-in-host-cell-glycolytic-metabolism
#3
Jordan V Price, Kallie Jiang, Abigail Galantowicz, Alana Freifeld, Russell E Vance
Toll-like receptor stimulation induces a pronounced shift to increased glycolytic metabolism in mammalian macrophages. We observed that bone marrow-derived macrophages (BMMs) increase glycolysis in response to infection with Legionella pneumophila ( L. pneumophila ), but the role of host macrophage glycolysis on intracellular L. pneumophila replication is not currently understood. Treatment with 2-deoxyglucose (2DG) blocks L. pneumophila replication in mammalian macrophages but has no effect on bacteria grown in broth...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29784770/tlr-activated-repression-of-fe-s-cluster-biogenesis-drives-a-metabolic-shift-and-alters-histone-and-tubulin-acetylation
#4
Wing-Hang Tong, Nunziata Maio, De-Liang Zhang, Erika M Palmieri, Hayden Ollivierre, Manik C Ghosh, Daniel W McVicar, Tracey A Rouault
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29783985/the-doses-of-plasmid-backbone-plays-a-major-role-in-determining-the-hbv-clearance-in-hydrodynamic-injection-mouse-model
#5
Xian Wang, Jianmin Zhu, Yong Zhang, Yue Li, Tai Ma, Qun Li, Jiegou Xu, Long Xu
BACKGROUND: Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. METHODS: In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence...
May 21, 2018: Virology Journal
https://www.readbyqxmd.com/read/29782532/hepatitis-c-virus-ns4b-induces-the-degradation-of-trif-to-inhibit-tlr3-mediated-interferon-signaling-pathway
#6
Yisha Liang, Xuezhi Cao, Qiang Ding, Yanan Zhao, Zhenliang He, Jin Zhong
Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781535/mir-1178-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages-partly-via-tlr4
#7
Ge Shi, Guofeng Mao, Kejie Xie, Dongdong Wu, Wei Wang
Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR-1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR-1178 in human macrophages (HTP-1 and U937 cells) in a concentration- and time-dependent manner...
May 21, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29780528/synthetic-glycan-based-tlr4-agonists-targeting-caspase-4-11-for-the-development-of-adjuvants-and-immunotherapeutics
#8
Florian Adanitsch, Jianjin Shi, Feng Shao, Rudi Beyaert, Holger Heine, Alla Zamyatina
Gram-negative bacterial lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4) mediated pro-inflammatory signaling plays a key role in immunoprotection against infectious challenges and boosts adaptive immunity, whereas the activation of the cytosolic LPS receptor caspase-4/11 leads to cell death by pyroptosis and is deeply implicated in the development of sepsis. Despite tremendous advances in the understanding of the LPS-TLR4 interaction, predictably regulated TLR4 activation has not yet been achieved...
April 28, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780321/toll-like-receptor-2-signaling-and-current-approaches-for-therapeutic-modulation-in-synucleinopathies
#9
REVIEW
Ian F Caplan, Kathleen A Maguire-Zeiss
The innate immune response in the central nervous system (CNS) is implicated as both beneficial and detrimental to health. Integral to this process are microglia, the resident immune cells of the CNS. Microglia express a wide variety of pattern-recognition receptors, such as Toll-like receptors, that detect changes in the neural environment. The activation of microglia and the subsequent proinflammatory response has become increasingly relevant to synucleinopathies, including Parkinson's disease the second most prevalent neurodegenerative disease...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29780305/comparing-effects-of-transforming-growth-factor-%C3%AE-1-on-microglia-from-rat-and-mouse-transcriptional-profiles-and-potassium-channels
#10
Starlee Lively, Doris Lam, Raymond Wong, Lyanne C Schlichter
The cytokine, transforming growth factor β1 (TGFβ1), is up-regulated after central nervous system (CNS) injuries or diseases involving microglial activation, and it has been proposed as a therapeutic agent for treating neuroinflammation. Microglia can produce and respond to TGFβ1. While rats and mice are commonly used for studying neuroinflammation, very few reports directly compare them. Such studies are important for improving pre-clinical studies and furthering translational progress in developing therapeutic interventions...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29779787/a-thermodynamic-funnel-drives-bacterial-lipopolysaccharide-transfer-in-the-tlr4-pathway
#11
Roland G Huber, Nils A Berglund, Vasileios Kargas, Jan K Marzinek, Daniel A Holdbrook, Syma Khalid, Thomas J Piggot, Artur Schmidtchen, Peter J Bond
The Gram-negative bacterial outer membrane contains lipopolysaccharide, which potently stimulates the mammalian innate immune response. This involves a relay of specialized complexes culminating in transfer of lipopolysaccharide from CD14 to Toll-like receptor 4 (TLR4) and its co-receptor MD-2 on the cell surface, leading to activation of downstream inflammatory responses. In this study we develop computational models to trace the TLR4 cascade in near-atomic detail. We demonstrate through rigorous thermodynamic calculations that lipopolysaccharide molecules traversing the receptor cascade fall into a thermodynamic funnel...
April 25, 2018: Structure
https://www.readbyqxmd.com/read/29779267/%C3%AE-synuclein-activates-innate-immunity-but-suppresses-interferon-%C3%AE-expression-in-murine-astrocytes
#12
Jintang Wang, Zheng Chen, Jeremy Walston, Peisong Gao, Maolong Gao, Sean X Leng
Glial activation and neuroinflammation contribute to pathogenesis of neurodegenerative diseases, linked to neuron loss and dysfunction. α-Synuclein (α-syn), as a metabolite of neuron, can induce microglia activation to trigger innate immune response. However, whether α-syn, as well as its mutants (A53T, A30P and E46K), induces astrocyte activation and inflammatory response is not fully elucidated. In this study, we used A53T mutant and wildtype α-syns to stimulate primary astrocytes in dose- and time-dependent manners (0...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29779263/effects-of-porphyromonas-gingivalis-lps-and-lr12-peptide-on-trem-1-expression-by-monocytes
#13
M Dubar, K Carrasco, S Gibot, C Bisson
Periodontal disease involves the activation of host immune response, acting not only as defender of periodontal tissues against bacterial aggression but also as mediator of tissue destruction. Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is an immune receptor that synergizes with Toll-like receptors in amplifying the inflammatory response mediated by microbial molecules. AIM: To investigate the role of P. gingivalis lipopolysaccharide (LPS) and the effect of LR12, a TREM-1 inhibitory peptide, on the expression of membrane-bound and soluble form of TREM-1 on human primary monocytes, as well as the production of pro-inflammatory cytokines...
May 19, 2018: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/29777767/biglycan-is-a-new-high-affinity-ligand-for-cd14-in-macrophages
#14
Heiko Roedig, Madalina V Nastase, Helena Frey, Kristin Moreth, Jinyang Zeng-Brouwers, Chiara Poluzzi, Louise Tzung-Harn Hsieh, Christian Brandts, Simone Fulda, Malgorzata Wygrecka, Liliana Schaefer
Sterile inflammation is a therapeutic target in many diseases where it represents an important initiator of disease progression. However, the detailed mechanisms underlying its evolution and biological relevance are not yet completely elucidated. Biglycan, a prototype extracellular matrix-derived damage-associated molecular pattern, mediates sterile inflammation in macrophages through Toll-like receptor (TLR) 2 and/or TLR4-dependent signaling pathways. Here we discovered that soluble biglycan is a novel high-affinity ligand for CD14, a well-known GPI-anchored co-receptor for TLRs...
May 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29777458/increased-vitamin-d-receptor-gene-expression-and-rs11568820-and-rs4516035-promoter-polymorphisms-in-autistic-disorder
#15
Burhan Balta, Hakan Gumus, Ruslan Bayramov, Keziban Korkmaz Bayramov, Murat Erdogan, Didem Behice Oztop, Muhammet Ensar Dogan, Serpil Taheri, Munis Dundar
Although there are a large number of sequence variants of different genes and copy number variations at various loci identified in autistic disorder (AD) patients, the pathogenesis of AD has not been elucidated completely. Recently, in AD patients, a large number of expression array and transcriptome studies have shown an increase in the expression of genes especially related to innate immune response. Antimicrobial effects of vitamin D and VDR are exerted through Toll-Like-Receptors (TLR) which have an important role in the innate immune response, are expressed by antigen presenting cells and recognize foreign microorganisms...
May 18, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29777026/endosomal-tlr3-tlr7-and-tlr8-control-neuronal-morphology-through-different-transcriptional-programs
#16
Yun-Fen Hung, Chiung-Ya Chen, Yi-Chun Shih, Hsin-Yu Liu, Chiao-Ming Huang, Yi-Ping Hsueh
Neuroinflammation is associated with diverse neurological disorders. Endosomal Toll-like receptors (TLRs) including TLR3, TLR7, and TLR8 cell-autonomously regulate neuronal differentiation. However, the mechanisms by which these three TLRs affect neuronal morphology are unclear. In this study, we compare these TLRs in mouse neurons. By combining in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling, we show that TLR8, TLR7, and TLR3 promote dendritic pruning via MYD88 signaling...
May 18, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29775741/replacement-of-fishmeal-by-spirulina-arthrospira-platensis-affects-growth-immune-related-gene-expression-in-gibel-carp-carassius-auratus-gibelio-var-cas-iii-and-its-challenge-against-aeromonas-hydrophila-infection
#17
Shenping Cao, Peiyu Zhang, Tao Zou, Shuzhan Fei, Dong Han, Junyan Jin, Haokun Liu, Yunxia Yang, Xiaoming Zhu, Shouqi Xie
The present study examined the effect of dietary spirulina, Arthrospira platensis on growth performance, blood physiological indices, immune-related gene expressions and resistance of juvenile gibel carp against Aeromonas hydrophila infection. Four isonitrogenous (360 g kg-1 ) and isolipidic (90 g kg-1 ) diets were formulated with containing different levels of spirulina powder of 0 g (SP0, the control diet), 3.38 g (SP3.38), 6.76 g (SP6.76) and 13.52 g (SP13.52) per 100 g diet to replace 0%, 25%, 50% and 100% of fishmeal protein, respectively...
May 15, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29775649/expression-and-function-of-tlr4-induced-b1r-bradykinin-receptor-on-cardiac-fibroblasts
#18
Claudia Muñoz-Rodríguez, Samuel Fernández, José Miguel Osorio, Francisco Olivares, Renatto Anfossi, Samir Bolivar, Claudio Humeres, Pía Boza, Raúl Vivar, Viviana Pardo-Jimenez, Karen E Hemmings, Neil A Turner, Guillermo Díaz-Araya
Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels...
May 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29775601/cells-stiffen-for-cytokines
#19
Richard Newton, Daniel J Müller
In this issue of Cell Chemical Biology, Knoops et al. (2018) use a novel approach in immunology: combining confocal microscopy and atomic force microscopy to unravel the specific interaction of oxidized peroxiredoxin-5 with Toll-like receptor 4 that leads to the release of interleukin-1β and the stiffening of mammalian cells.
May 17, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29774159/toll-like-receptors-2-and-4-modulate-intestinal-il-10-differently-in-ileum-and-colon
#20
Eva Latorre, Elena Layunta, Laura Grasa, Julián Pardo, Santiago García, Ana I Alcalde, José E Mesonero
Background: Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis...
April 2018: United European Gastroenterology Journal
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