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https://www.readbyqxmd.com/read/29453396/bone-marrow-lympho-myeloid-malfunction-in-obesity-requires-precursor-cell-autonomous-tlr4
#1
Ailing Liu, Minhui Chen, Rashmi Kumar, Maja Stefanovic-Racic, Robert M O'Doherty, Ying Ding, Willi Jahnen-Dechent, Lisa Borghesi
Obesity, a prevalent condition in adults and children, impairs bone marrow (BM) function. However, the underlying mechanisms are unclear. Here, we show that obese mice exhibit poor emergency immune responses in a toll-like receptor 4 (TLR4)-dependent manner. Canonical myeloid genes (Csf1r, Spi1, Runx1) are enhanced, and lymphoid genes (Flt3, Tcf3, Ebf1) are reduced. Using adoptive transfer and mixed BM chimera approaches we demonstrate that myeloid>lymphoid bias arises after 6 weeks of high-fat diet and depends on precursor cell-autonomous TLR4...
February 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29452802/moving-to-human-trials-for-argon-neuroprotection-in-neurological-injury-a-narrative-review
#2
REVIEW
A J Gardner, D K Menon
Despite the global burden of brain injury, neuroprotective agents remain elusive. There are no clinically effective therapies which reduce mortality or improve long-term cognitive outcome. Ventilation could be an easily modifiable variable in resuscitation; gases are relatively simple to administer. Xenon is the prototypic agent of a new generation of experimental treatments which show promise. However, use is hindered by its prohibitive cost and anaesthetic properties. Argon is an attractive option, being cheaper, easy to transport, non-sedating, and mechanistically distinct from xenon...
March 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29452403/mechanisms-controlling-nucleic-acid-sensing-toll-like-receptors
#3
Kensuke Miyake, Takuma Shibata, Umeharu Ohto, Toshiyuki Shimizu, Shin-Ichiroh Saitoh, Ryutaro Fukui, Yusuke Murakami
Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and 8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization...
February 14, 2018: International Immunology
https://www.readbyqxmd.com/read/29452288/repetitive-tlr-3-activation-in-the-lung-induces-skeletal-muscle-adaptations-and-cachexia
#4
Ted G Graber, Brandy L Rawls, Bing Tian, William J Durham, Camille R Brightwell, Allan R Brasier, Blake B Rasmussen, Christopher S Fry
Due to immunosenescence, older adults are particularly susceptible to lung-based viral infections, with increased severity of symptoms in those with underlying chronic lung disease. Repeated respiratory viral infections produce lung maladaptations, accelerating pulmonary dysfunction. Toll like 3 receptor (TLR3) is a membrane protein that senses exogenous double-stranded RNA to activate the innate immune response to a viral infection. Polyinosinic-polycytidylic acid [poly(I:C)] mimics double stranded RNA and has been shown to activate TLR3...
February 13, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29452258/recent-findings-related-to-immune-responses-against-leptospirosis-and-novel-strategies-to-prevent-infection
#5
Frédérique Vernel-Pauillac, Catherine Werts
What are the new approaches and emerging ideas to prevent leptospirosis, a neglected bacterial re-emerging zoonotic disease? How do Leptospira interrogans escape the host defenses? We aim here to review and discuss the most recent literature that provides some answers to these questions, in particular data related to a better understanding of adaptive and innate immunity towards leptospires, and design of vaccines. This is an opinion paper, not a comprehensive review. We will try to highlight the new strategies and technologies boosting the search for drugs and vaccines...
February 13, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29452196/staphylococcus-aureus-induces-tgf-%C3%AE-1-and-bfgf-expression-through-the-activation-of-ap-1-and-nf-%C3%AE%C2%BAb-transcription-factors-in-bovine-mammary-epithelial-cells
#6
Jianmei Wu, Yulin Ding, Jinling Wang, Fenglong Wang
Staphylococcus aureus is a common Gram-positive pathogen that causes bovine mastitis, a persistent infection of the bovine mammary gland. Bovine mammary epithelial cells (BMEC) are important parenchymal cells of the bovine mammary gland. To better understand the importance of BMEC and the roles of the TLR-NF-κBand TLR-AP-1 signaling pathways in the regulation of S. aureus-associated mastitis and mammary fibrosis, BMEC cultured in vitro were stimulated with different concentrations of heat-inactivated S. aureus to analyze the gene and protein expression and production of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF) as well as the protein expression of nuclear factor-kappa B (NF-κB) and activation protein-1 (AP-1) by means of quantitative polymerase chain reaction (qPCR) and western blotting, respectively...
February 13, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29452169/expression-patterns-of-toll-like-receptor-tlr-2-tlr-4-and-myeloid-differentiation-primary-response-gene-88-myd88-in-renal-transplant-patients-developing-allograft-dysfunction-a-cohort-study
#7
Morteza Hosseinzadeh, Pedram Ahmadpoor, Mir Saeed Yekaninejad, Fatemeh Pourrezagholi, Farshad Foroughi, Mina Ghorbanpour, Mehri Barabadi, Sanaz K Shahbaz, Ghasem Solgi, Aliakbar Amirzargar
This cohort intends to determine the sequential dynamic changes in Toll-like receptor (TLR)-4, TLR-2, and myeloid differentiation primary response gene 88 (MYD88) mRNA expressions in PBMCs and biopsy samples from kidney allograft recipients in relation to graft function. This study enrolled 52 renal transplant patients, 27 with well functioning graft (WFG) and 25 graft dysfunction (GD). Peripheral blood samples pre- and post-transplantation (days 2, 90 and 180) were collected to analyze mRNA expression levels of TLR-2, TLR-4, and MYD88 genes in relation to allograft function during one-year follow up...
February 13, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29451405/astragalus-polysaccharide-alleviates-lps-induced-inflammation-injury-by-regulating-mir-127-in-h9c2-cardiomyoblasts
#8
Qi Ren, Shaojun Zhao, Changjie Ren, Zhen Ma
Astragalus polysaccharide (APS) has been widely reported to play an important role in inflammatory response. In this study, we aimed to explore the effects and underlying mechanisms of APS on lipopolysaccharide (LPS)-induced inflammation injury in H9c2 cardiomyoblasts. H9c2 cells were treated with different concentrations of APS, and cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay. Then, the effect of APS on cell viability and apoptosis induced by LPS was determined by CCK-8, flow cytometry, and western blot...
January 2018: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29450964/imparting-designer-biorecognition-functionality-to-metal-organic-frameworks-by-a-dna-mediated-surface-engineering-strategy
#9
Weiyu Ning, Zhenghan Di, Yingjie Yu, Pingmei Zeng, Chunzhi Di, Daquan Chen, Xueqian Kong, Guangjun Nie, Yuliang Zhao, Lele Li
Surface functionality is an essential component for processing and application of metal-organic frameworks (MOFs). A simple and cost-effective strategy for DNA-mediated surface engineering of zirconium-based nanoscale MOFs (NMOFs) is presented, capable of endowing them with specific molecular recognition properties and thus expanding their potential for applications in nanotechnology and biotechnology. It is shown that efficient immobilization of functional DNA on NMOFs can be achieved via surface coordination chemistry...
February 16, 2018: Small
https://www.readbyqxmd.com/read/29450641/chronic-lymphocytic-leukemia-cells-acquire-regulatory-b-cell-properties-in-response-to-tlr9-and-cd40-activation
#10
Shimrit Ringelstein-Harlev, Irit Avivi, Mona Fanadka, Netanel A Horowitz, Tami Katz
Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia...
February 15, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29450541/induction-of-ocular-complement-activation-by-inflammatory-stimuli-and-intraocular-inhibition-of-complement-factor-d-in-animal-models
#11
Maura A Crowley, Omar Delgado, Adrian Will-Orrego, Natasha M Buchanan, Karen Anderson, Bruce D Jaffee, Thaddeus P Dryja, Sha-Mei Liao
Purpose: Genome-wide association studies suggest a role for the complement system in age-related macular degeneration (AMD). We characterized ocular complement activation and evaluated a complement factor D (FD) neutralizing antibody. Methods: Mice were treated with toll-like receptor (TLR) ligands, intravitreal injection (IVT), or corneal debridement. Levels of complement proteins and mRNA were measured. A FD neutralizing antibody was administered IVT into eyes of rabbits that were challenged with LPS (lipopolysaccharide) administered intravenously...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29449668/rhinovirus-3c-protease-suppresses-apoptosis-and-triggers-caspase-independent-cell-death
#12
Mark Lötzerich, Pascal S Roulin, Karin Boucke, Robert Witte, Oleg Georgiev, Urs F Greber
Apoptosis and programmed necrosis (necroptosis) determine cell fate, and antagonize infection. Execution of these complementary death pathways involves the formation of receptor-interacting protein kinase 1 (RIPK1) containing complexes. RIPK1 binds to adaptor proteins, such as TRIF (Toll-IL-1 receptor-domain-containing-adaptor-inducing interferon-beta factor), FADD (Fas-associated-protein with death domain), NEMO (NF-κB regulatory subunit IKKγ), SQSTM1 (sequestosome 1/p62), or RIPK3 (receptor-interacting protein kinase 3), which are involved in RNA sensing, NF-κB signaling, autophagosome formation, apoptosis, and necroptosis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449625/toll-like-receptor-4-modulation-influences-human-neural-stem-cell-proliferation-and-differentiation
#13
Chiara Grasselli, Daniela Ferrari, Cristina Zalfa, Matias Soncini, Gianluigi Mazzoccoli, Fabio A Facchini, Laura Marongiu, Francesca Granucci, Massimiliano Copetti, Angelo Luigi Vescovi, Francesco Peri, Lidia De Filippis
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29448819/identifying-the-inhibition-of-tir-proteins-involved-in-tlr-signalling-as-an-anti-inflammatory-strategy
#14
U Saqib, M S Baig
Toll/IL1 receptor (TIR) adaptor proteins continue to be an integral part of Toll-like receptors' (TLR) signalling involved in inflammation. Signalling is likely to be initiated by these TIR adaptors when they are recruited to a TIR-TIR interface formed by TLR dimerization. Among these, myeloid differentiation factor-88 (MyD88), MyD88 adapter-like protein (Mal), TIR domain-containing adaptor protein inducing interferon-β (TRIF) and TRIF-related adaptor molecule (TRAM) play pivotal roles at many steps in the signalling events leading to inflammation...
February 15, 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29447335/condition-dependent-generation-of-aquaporin-4-antibodies-from-circulating-b-cells-in-neuromyelitis-optica
#15
Robert Wilson, Mateusz Makuch, Anne-Kathrin Kienzler, James Varley, Jennifer Taylor, Mark Woodhall, Jacqueline Palace, M Isabel Leite, Patrick Waters, Sarosh R Irani
Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica spectrum disorder (NMOSD). However, it is not known which B cells are the major contributors to circulating AQP4 antibodies nor which conditions promote their generation. Our experiments showed CD19+CD27++CD38++ circulating ex vivo antibody-secreting cells did not produce AQP4 antibodies under several culture conditions. To question whether other cells in circulation were capable of AQP4 antibody production, B cells were differentiated into antibody-secreting cells in vitro...
February 13, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29447283/gp96-deficiency-affects-tlr4-functionality-and-impairs-erk-and-p38-phosphorylation
#16
Jesus Cosin-Roger, Marianne R Spalinger, Pedro A Ruiz, Claudia Stanzel, Anne Terhalle, Lutz Wolfram, Hassan Melhem, Kirstin Atrott, Silvia Lang, Isabelle Frey-Wagner, Michael Fried, Michael Scharl, Martin Hausmann, Gerhard Rogler
Gp96 is an endoplasmic reticulum chaperone for multiple protein substrates. Its lack in intestinal macrophages of Crohn's disease (CD) patients is correlated with loss of tolerance against the host gut flora. Gp96 has been stablished to be an essential chaperone for Toll-like receptors (TLRs). We studied the impact of gp96-knockdown on TLR-function in macrophages. TLR2 and TLR4 expression was only decreased but not abolished when gp96 was knocked-down in cell lines, whereas in a monocyte/macrophage specific knock-out mouse model (LysMCre) TLR4 was abolished, while TLR2 was still present...
2018: PloS One
https://www.readbyqxmd.com/read/29447181/innate-immune-responses-following-kawasaki-disease-and-toxic-shock-syndrome
#17
Katherine Y H Chen, Nicole Messina, Susie Germano, Rhian Bonnici, Bridget Freyne, Michael Cheung, Greta Goldsmith, Tobias R Kollmann, Michael Levin, David Burgner, Nigel Curtis
The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly...
2018: PloS One
https://www.readbyqxmd.com/read/29445128/the-brace-helices-of-mlkl-mediate-interdomain-communication-and-oligomerisation-to-regulate-cell-death-by-necroptosis
#18
Katherine A Davies, Maria C Tanzer, Michael D W Griffin, Yee Foong Mok, Samuel N Young, Rui Qin, Emma J Petrie, Peter E Czabotar, John Silke, James M Murphy
The programmed cell death pathway, necroptosis, relies on the pseudokinase, Mixed Lineage Kinase domain-Like (MLKL), for cellular execution downstream of death receptor or Toll-like receptor ligation. Receptor-interacting protein kinase-3 (RIPK3)-mediated phosphorylation of MLKL's pseudokinase domain leads to MLKL switching from an inert to activated state, where exposure of the N-terminal four-helix bundle (4HB) 'executioner' domain leads to cell death. The precise molecular details of MLKL activation, including the stoichiometry of oligomer assemblies, mechanisms of membrane translocation and permeabilisation, remain a matter of debate...
February 14, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29444515/comprehensive-mirna-analysis-of-human-umbilical-cord-derived-mesenchymal-stromal-cells-and-extracellular-vesicles
#19
Xiang-Yu Zou, Yongjiang Yu, Sihao Lin, Liang Zhong, Jie Sun, Guangyuan Zhang, Yingjian Zhu
BACKGROUND/AIMS: Mesenchymal stromal cells (MSCs) participate in the tissue-specific repair of many different organs, especially the kidney. Their effects are primarily mediated by the paracrine release of factors including extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes. The corresponding microRNAs (miRNAs) of EVs are considered important for their biological functions. METHODS: MSCs were cultured from the human umbilical cord, and EVs were isolated from the medium...
February 8, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29441063/toll-like-receptors-and-inflammatory-bowel-disease
#20
REVIEW
Yue Lu, Xinrui Li, Shanshan Liu, Yifan Zhang, Dekai Zhang
Inflammatory bowel disease (IBD) is one relapsing and lifelong disease that affects millions of patients worldwide. Increasing evidence has recently highlighted immune-system dysfunction, especially toll-like receptors (TLRs)-mediated innate immune dysfunction, as central players in the pathogenesis of IBD. TLRs and TLR-activated signaling pathways are involved not only in the pathogenesis but also in the efficacy of treatment of IBD. By understanding these molecular mechanisms, we might develop a strategy for relieving the experience of long-lasting suffering of those patients and improving their quality of life...
2018: Frontiers in Immunology
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