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https://www.readbyqxmd.com/read/29156775/monophosphoryl-lipid-a-attenuates-radiation-injury-through-tlr4-activation
#1
Jiaming Guo, Yuanyuan Chen, Xiao Lei, Yang Xu, Zhe Liu, Jianming Cai, Fu Gao, Yanyong Yang
Ionizing radiation causes severe damage to human body, and normal tissue toxicity in cancer radiotherapy also limits its further application. It is urgently required to develop safe and effective radioprotector. Our previous study has shown that toll like receptor 4 (TLR4) was dispensable for basal radiation resistance. However, severe toxicity of its traditional agonist lipopolysaccharide limits the clinical application. In present study, we demonstrated that monophosphoryl lipid A (MPLA), a potent TLR4 agonist with low toxicity, effectively attenuated radiation injury on in vitro and in vivo...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29142761/aeromonas-hydrophila-utilizes-tlr4-topology-for-synchronous-activation-of-myd88-and-trif-to-orchestrate-anti-inflammatory-responses-in-zebrafish
#2
Nidhi Srivastava, Asha Shelly, Manmohan Kumar, Archana Pant, Bhabatosh Das, Tanmay Majumdar, Shibnath Mazumder
Toll-like receptor 4 (TLR4) plays a critical role in host immunity against Gram-negative bacteria. It transduces signals through two distinct TIR-domain-containing adaptors, MyD88 and TRIF, which function at the plasma membrane and endosomes, respectively. Using zebrafish Aeromonas hydrophila infection model, we demonstrate that synchronization of MyD88 and TRIF dependent pathways is critical for determining the fate of infection. Zebrafish were infected with A. hydrophila, and bacterial recovery studies suggested its effective persistence inside the host...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29116594/elevated-expression-of-ebv-and-tlrs-in-the-brain-is-associated-with-rasmussen-s-encephalitis
#3
Xin Wang, Yisong Wang, Dong Liu, Peigang Wang, Dongying Fan, Yuguang Guan, Tianfu Li, Guoming Luan, Jing An
Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus (EBV) antigens as well as of Toll-like receptor 3 (TLR3), TLR9, and downstream adapter TIRdomain-containing adapter-inducing interferon-β (TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry (IHC)...
October 2017: Virologica Sinica
https://www.readbyqxmd.com/read/29115392/the-inhibition-of-myd88-and-trif-signaling-serve-equivalent-roles-in-attenuating-myocardial-deterioration-due-to-acute-severe-inflammation
#4
Min-Zhi Ouyang, Dan Zhou, Yun Zhu, Ming Zhang, Ling Li
Myeloid differentiation factor 88 (MyD88) and Toll or interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (IFN-β) (TRIF) are two pivotal downstream adaptors of Toll-like receptors. Activation of MyD88 or TRIF signaling in cardiac immune pathology of severe inflammation negatively influences heart function. In the present study, severe septic cardiac injury was induced in C57BL/6 mice by cecum ligation and puncture (CLP). A total of 64 mice were divided randomly into the following four groups (n=16/group; 8 for observation of survival rate, 8 for heart sample analysis): Sham, CLP, anti-MyD88-CLP and anti-TRIF-CLP...
November 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29114065/bim-suppresses-the-development-of-sle-by-limiting-myeloid-inflammatory-responses
#5
FuNien Tsai, Philip J Homan, Hemant Agrawal, Alexander V Misharin, Hiam Abdala-Valencia, G Kenneth Haines, Salina Dominguez, Christina L Bloomfield, Rana Saber, Anthony Chang, Chandra Mohan, Jack Hutcheson, Anne Davidson, G R Scott Budinger, Philippe Bouillet, Andrea Dorfleutner, Christian Stehlik, Deborah R Winter, Carla M Cuda, Harris Perlman
The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. We demonstrate that Bim acts as a molecular rheostat by controlling macrophage function not only in lymphoid organs but also in end organs, thereby preventing the break in tolerance. Mice lacking Bim in myeloid cells (LysM(Cre)Bim(fl/fl)) develop a systemic lupus erythematosus (SLE)-like disease that mirrors aged Bim(-/-) mice, including loss of marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies (including anti-DNA IgG), and a type I interferon signature...
November 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29113305/vinpocetine-alleviate-cerebral-ischemia-reperfusion-injury-by-down-regulating-tlr4-myd88-nf-%C3%AE%C2%BAb-signaling
#6
Li-Rong Wu, Liang Liu, Xiao-Yi Xiong, Qin Zhang, Fa-Xiang Wang, Chang-Xiong Gong, Qi Zhong, Yuan-Rui Yang, Zhao-You Meng, Qing-Wu Yang
Inflammatory responses play crucial roles in cerebral ischemia/reperfusion injury. Toll-like receptor 4 (TLR4) is an important mediator of the neuroinflammatory response to cerebral ischemia/reperfusion injury. Vinpocetine is a derivative of the alkaloid vincamine and exerts an anti-inflammatory effect by inhibiting NF-κB activation. However, the effects of vinpocetine on pathways upstream of NF-κB signaling, such as TLR4, have not been fully elucidated. Here, we used mouse middle cerebral artery occlusion (MCAO) and cell-based oxygen-glucose deprivation (OGD) models to evaluate the therapeutic effects and mechanisms of vinpocetine treatment...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110678/utilization-of-biodiesel-derived-glycerol-for-1-3-pd-and-citric-acid-production
#7
REVIEW
Laura Mitrea, Monica Trif, Adriana-Florinela Cătoi, Dan-Cristian Vodnar
Today, biofuels represent a hot topic in the context of petroleum and adjacent products decrease. As biofuels production increase, so does the production of their major byproduct, namely crude glycerol. The efficient usage of raw glycerol will concur to the biodiesel viability. As an inevitable waste of biodiesel manufacturing, glycerol is potentially an attractive substrate for the production of value-added products by fermentation processes, due to its large amounts, low cost and high degree of reduction...
November 6, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29107214/tim-3-enhances-brain-inflammation-by-promoting-m1-macrophage-polarization-following-intracerebral-hemorrhage-in-mice
#8
Anyong Yu, Xiaojun Zhang, Mo Li, Peng Ye, Haizhen Duan, Tianxi Zhang, Zhao Yang
Macrophage polarization contributes to brain inflammation following spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) has been identified to induce macrophage mediated inflammation following ICH. However, the regulation of Tim-3 on macrophage polarization following ICH has not been fully studied. In current experiment, we explored Tim-3 expression, macrophage polarization, brain water content and neurological function in WT and Tim-3(-)/(-) ICH mice. In addition, downstream transcriptional factor TRIF and IRF3 were also analyzed...
October 26, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29059681/protective-effect-of-phillyrin-on-lethal-lps-induced-neutrophil-inflammation-in-zebrafish
#9
Liling Yang, Xiangjun Zhou, Weijuan Huang, Qin Fang, Jianlan Hu, Linzhong Yu, Ning Ma, Wenqing Zhang
BACKGROUND/AIMS: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish...
October 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29046251/mycobacterium-tuberculosis-esat6-induces-ifn-%C3%AE-gene-expression-in-macrophages-via-tlrs-mediated-signaling
#10
Ah-Ra Jang, Joo-Hee Choi, Sung Jae Shin, Jong-Hwan Park
Mycobacterium tuberculosis is a highly virulent bacterium that causes tuberculosis. It infects about one third of the world's population. Type I interferons (IFNs) play a detrimental role in host defense against M. tuberculosis infection. Proteins secreted by M. tuberculosis through ESX-1 secretion system contribute to type I IFNs production. However, the precise mechanism by which 6-kDa early secretory antigen target (ESAT6), one of ESX-1-mediated secretory proteins, induces type I IFNs production in host cells is currently unclear...
October 15, 2017: Cytokine
https://www.readbyqxmd.com/read/29041928/the-tlr3-ticam-1-signal-constitutively-controls-spontaneous-polyposis-through-suppression-of-c-myc-in-apc-min-mice
#11
Junya Ono, Hiroaki Shime, Hiromi Takaki, Ken Takashima, Kenji Funami, Sumito Yoshida, Yohei Takeda, Misako Matsumoto, Masanori Kasahara, Tsukasa Seya
BACKGROUND: Intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (MyD88) activation in response to the components of microbiota in Apc (Min/+) mice. Microbiota also contains double-stranded RNA (dsRNA), a ligand for TLR3, which activates the toll-like receptor adaptor molecule 1 (TICAM-1, also known as TRIF) pathway. METHODS: We established Apc (Min/+) Ticam1 (-/-) mice and their survival was compared to survival of Apc (Min/+) Myd88 (-/-) and wild-type (WT) mice...
October 17, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28976923/tlr4-signaling-pathway-modulators-as-potential-therapeutics-in-inflammation-and-sepsis
#12
REVIEW
Nikolay N Kuzmich, Konstantin V Sivak, Vladimir N Chubarev, Yuri B Porozov, Tatiana N Savateeva-Lyubimova, Francesco Peri
Toll-Like Receptor 4 (TLR4) signal pathway plays an important role in initiating the innate immune response and its activation by bacterial endotoxin is responsible for chronic and acute inflammatory disorders that are becoming more and more frequent in developed countries. Modulation of the TLR4 pathway is a potential strategy to specifically target these pathologies. Among the diseases caused by TLR4 abnormal activation by bacterial endotoxin, sepsis is the most dangerous one because it is a life-threatening acute system inflammatory condition that still lacks specific pharmacological treatment...
October 4, 2017: Vaccines
https://www.readbyqxmd.com/read/28974092/poly-i-c-encapsulating-nanoparticles-enhance-innate-immune-responses-to-the-tuberculosis-vaccine-bacille-calmette-gu%C3%A3-rin-bcg-via-synergistic-activation-of-innate-immune-receptors
#13
Martin T Speth, Urska Repnik, Elisabeth Müller, Julia Spanier, Ulrich Kalinke, Alexandre Corthay, Gareth Griffiths
The attenuated live vaccine strain bacille Calmette-Guérin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG's ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3), to enhance the immunogenicity of BCG in mouse bone marrow derived macrophages (BMDM) in vitro...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28969526/evaluating-mrna-expression-levels-of-the-tlr4-irf5-signaling-axis-during-hepatic-ischemia-reperfusion-injuries
#14
Meysam Nasiri, Mostafa Saadat, Mohammad-Hossein Karimi, Negar Azarpira, Iraj Saadat
OBJECTIVES: Hepatic ischemia and reperfusion during liver transplant surgery result in hepatocellular damage. Toll-like receptors, especially TLR4, have a fundamental basic role in the inflammatory phase of ischemia-reperfusion injuries. The effect of the TRIF-dependent signaling pathway downstream of TLR4 in hepatic ischemia-reperfusion injury has been well established. However, the role of TLR4-MyD88-dependent signal transduction in hepatic ischemia-reperfusion injury has not yet been clarified...
September 30, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28964858/expression-and-functional-characterization-of-trif-in-orange-spotted-grouper-epinephelus-coioides
#15
Jingguang Wei, Xin Zhang, Shaoqing Zang, Qiwei Qin
Antiviral immune responses are triggered by the innate immune recognition of viral infection. Toll/interleukin-1 receptor (TIR) domain containing adapter inducing interferon-β (TRIF) is an adapter in responding to activation of Toll-like receptors, which provides early clearance of viral pathogens. Our study focuses on the functional characterization of grouper TRIF (EcTRIF) based on the comparison of its sequence and functional evolution from grouper fish to mammals. The results show that the open reading frame of EcTRIF encoded a protein of 580 amino acids...
September 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28950845/ethanol-extract-of-propolis-and-its-constituent-caffeic-acid-phenethyl-ester-inhibit-breast-cancer-cells-proliferation-in-inflammatory-microenvironment-by-inhibiting-tlr4-signal-pathway-and-inducing-apoptosis-and-autophagy
#16
Huasong Chang, Yuehua Wang, Xusheng Yin, Xinying Liu, Hongzhuan Xuan
BACKGROUND: Propolis and its major constituent - caffeic acid phenethyl ester (CAPE) have good abilities on antitumor and anti-inflammation. However, little is known about the actions of propolis and CAPE on tumor in inflammatory microenvironment, and inflammatory responses play decisive roles at different stages of tumor development. To understand the effects and mechanisms of ethanol-extracted Chinese propolis (EECP) and its major constituent - CAPE in inflammation-stimulated tumor, we investigated their effects on Toll-like receptor 4 (TLR4) signaling pathway which plays a crucial role in breast cancer MDA-MB-231 cell line...
September 26, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28947376/antagonising-tlr4-trif-signalling-before-or-after-a-low-dose-alcohol-binge-during-adolescence-prevents-alcohol-drinking-but-not-seeking-behaviour-in-adulthood
#17
Jonathan Henry Jacobsen, Femke Buisman-Pijlman, Sanam Mustafa, Kenner C Rice, Mark R Hutchinson
Adolescents frequently engage in risky behaviours such as binge drinking. Binge drinking, in turn, perturbs neurodevelopment reinforcing reward seeking behaviour in adulthood. Current animal models are limited in their portrayal of this behaviour and the assessment of neuroimmune involvement (specifically the role of Toll-like receptor 4 (TLR4)). Therefore, the aims of this project were to develop a more relevant animal model of adolescent alcohol exposure and to characterise its effects on TLR4 signalling and alcohol-related behaviours later life...
September 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28945004/tlr3-contributes-to-persistent-autophagy-and-heart-failure-in-mice-after-myocardial-infarction
#18
Ting Gao, Shao-Ping Zhang, Jian-Fei Wang, Li Liu, Yin Wang, Zhi-Yong Cao, Qi-Kuan Hu, Wen-Jun Yuan, Li Lin
Toll-like receptors (TLRs) are essential immunoreceptors involved in host defence against invading microbes. Recent studies indicate that certain TLRs activate immunological autophagy to eliminate microbes. It remains unknown whether TLRs regulate autophagy to play a role in the heart. This study examined this question. The activation of TLR3 in cultured cardiomyocytes was observed to increase protein levels of autophagic components, including LC3-II, a specific marker for autophagy induction, and p62/SQSTM1, an autophagy receptor normally degraded in the final step of autophagy...
September 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28912382/versican-is-produced-by-trif-and-type-i-interferon-dependent-signaling-in-macrophages-and-contributes-to-fine-control-of-innate-immunity-in-lungs
#19
Mary Y Chang, Inkyung Kang, Michael Gale, Anne M Manicone, Michael G Kinsella, Kathleen R Braun, Tara Wigmosta, William C Parks, William A Altemeier, Thomas N Wight, Charles W Frevert
Growing evidence suggests that versican is important in the innate immune response to lung infection. Our goal was to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. We first defined the signaling events that regulate versican expression using bone marrow derived macrophages (BMDM) from mice lacking specific Toll-like receptors (TLR), TLR adaptor molecules or the type I interferon receptor (IFNAR1). We show that LPS and polyinosinic-polycytidylic acid [Poly(I:C)] trigger a signaling cascade involving TLR3 or 4, the Trif adaptor, Type I interferons and IFNAR1, leading to increased expression of versican by macrophages and implicating versican as an interferon-stimulated gene...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28898289/trim32-tax1bp1-dependent-selective-autophagic-degradation-of-trif-negatively-regulates-tlr3-4-mediated-innate-immune-responses
#20
Qing Yang, Tian-Tian Liu, Heng Lin, Man Zhang, Jin Wei, Wei-Wei Luo, Yun-Hong Hu, Bo Zhong, Ming-Ming Hu, Hong-Bing Shu
Toll-like receptor (TLR)-mediated signaling are critical for host defense against pathogen invasion. However, excessive responses would cause harmful damages to the host. Here we show that deficiency of the E3 ubiquitin ligase TRIM32 increases poly(I:C)- and LPS-induced transcription of downstream genes such as type I interferons (IFNs) and proinflammatory cytokines in both primary mouse immune cells and in mice. Trim32-/- mice produced higher levels of serum inflammatory cytokines and were more sensitive to loss of body weight and inflammatory death upon Salmonella typhimurium infection...
September 2017: PLoS Pathogens
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