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https://www.readbyqxmd.com/read/29276218/signal-diversity-of-receptor-for-advanced-glycation-end-products
#1
REVIEW
Masakiyo Sakaguchi, Rie Kinoshita, Endy Widya Putranto, I Made Winarsa Ruma, I Wayan Sumardika, Chen Youyi, Naoko Tomonobu, Ken-Ichi Yamamoto, Hitoshi Murata
The receptor for advanced glycation end products (RAGE) is involved in inflammatory pathogenesis. It functions as a receptor to multiple ligands such as AGEs, HMGB1 and S100 proteins, activating multiple intracellular signaling pathways with each ligand binding. The molecular events by which ligand-activated RAGE controls diverse signaling are not well understood, but some progress was made recently. Accumulating evidence revealed that RAGE has multiple binding partners within the cytoplasm and on the plasma membrane...
December 2017: Acta Medica Okayama
https://www.readbyqxmd.com/read/29229676/teleost-specific-tlr19-localizes-to-endosome-recognizes-dsrna-recruits-trif-triggers-both-ifn-and-nf-%C3%AE%C2%BAb-pathways-and-protects-cells-from-grass-carp-reovirus-infection
#2
Jianfei Ji, Youliang Rao, Quanyuan Wan, Zhiwei Liao, Jianguo Su
TLRs are pivotal pattern recognition receptors in initiating innate immunity and triggering adaptive immunity. TLR pathways have been comprehensively investigated in mammals. However, the teleost-specific TLR19 pathway remains largely unknown. In this study, we identified TLR19 from grass carp (Ctenopharyngodon idella), and explored the ligand, adaptor, and signaling pathways. Pathogen-associated molecular pattern binding and luciferase activity assays indicate that TLR19 recognizes and responds to dsRNA analog (polyinosinic:polycytidylic acid)...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29222167/cytoplasmic-linker-protein-clip170-negatively-regulates-tlr4-signaling-by-targeting-the-tlr-adaptor-protein-tirap
#3
Padmaja Jakka, Bindu Bhargavi, Swapna Namani, Subathra Murugan, Gary Splitter, Girish Radhakrishnan
Cytoplasmic linker protein 170 (CLIP170) is a CAP-Gly domain-containing protein that is associated with the plus end of growing microtubules and implicated in various cellular processes, including the regulation of microtubule dynamics, cell migration, and intracellular transport. Our studies revealed a previously unrecognized property and role of CLIP170. We identified CLIP170 as one of the interacting partners of Brucella effector protein TcpB that negatively regulates TLR2 and TLR4 signaling. In this study, we demonstrate that CLIP170 interacts with the TLR2 and TLR4 adaptor protein TIRAP...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29179209/calycosin-suppresses-epithelial-derived-initiative-key-factors-and-maintains-epithelial-barrier-in-allergic-inflammation-via-tlr4-mediated-nf-%C3%AE%C2%BAb-pathway
#4
Yu Tao, Yan Wang, Xiaoyu Wang, Can Wang, Kaifang Bao, Lv Ji, Guorong Jiang, Min Hong
BACKGROUND/AIMS: Calycosin is a bioactive component of Astragali Radix, a Chinese herb for treating allergy. We have previously demonstrated that calycosin effectively inhibited allergic inflammation efficiently. The aim of this study was to explore the mechanism of calycosin on epithelial cells in allergic inflammation. METHODS: An initial stage of atopic dermatitis (AD) model in which mice were just sensitized with FITC, was established in vivo and immortalized human keratinocytes (HaCaT cells) were utilized in vitro...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29177857/biochemical-isolation-of-the-myddosome-from-murine-macrophages
#5
Yunhao Tan, Jonathan C Kagan
Ligand-induced macromolecular protein complex formation has emerged as a common means by which the innate immune system activates signal transduction pathways essential for host defense. Despite their structural divergence, key signaling molecules in diverse innate immune pathways mediate signal transduction by assembling higher-order protein complexes at specific subcellular locations in a stimulus-dependent manner. These protein complexes are collectively known as the supramolecular organizing centers (SMOCs), which link active receptors to a variety of downstream cellular responses...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29175418/src-family-kinase-tyrosine-phosphorylates-toll-like-receptor-4-to-dissociate-myd88-and-mal-tirap-suppressing-lps-induced-inflammatory-responses
#6
Jonathon Mitchell, Su Jin Kim, Alexandra Seelmann, Brendan Veit, Brooke Shepard, Eunok Im, Sang Hoon Rhee
Src family kinases (SFKs) are a family of protein tyrosine kinases containing nine members: Src, Lyn, Fgr, Hck, Lck, Fyn, Blk, Yes, and Ylk. Although SFK activation is a major immediate signaling event in LPS/Toll-like receptor 4 (TLR4) signaling, its precise role has remained elusive due to various contradictory results obtained from a certain SFK member-deficient mice or cells. The observed inconsistencies may be due to the compensation or redundancy by other SFKs upon a SFK deficiency. The chemical rescuing approach was suggested to induce temporal and precise SFK activation in living cells, thereby limiting the chance of cellular adaption to a SFK-deficient condition...
November 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29121163/gene-expression-profiling-reveals-heterogeneity-of-perivascular-adipose-tissues-surrounding-coronary-and-internal-thoracic-arteries
#7
Danbo Lu, Wei Wang, Limin Xia, Pu Xia, Yan Yan
The internal thoracic artery (ITA) that differs from coronary artery (CA), rarely develops atherosclerosis. Understanding the mechanism underlying such a difference will help to pave a new way to the prevention and treatment of the disease. We hypothesize herein that the difference in susceptibility to atherosclerosis between CA and ITA is attributable to the heterogeneity of perivascular adipose tissues (PVATs) surrounding these two kinds of arteries, i.e. PVAT-CA and PVAT-ITA. We isolated PVAT from eight patients of coronary heart disease (CHD) and four non-CHD patients...
November 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29119782/intracellular-protein-labeling-probes-for-multicolor-single-molecule-imaging-of-immune-receptor-adaptor-molecular-dynamics
#8
Ryota Sato, Jun Kozuka, Masahiro Ueda, Reiko Mishima, Yutaro Kumagai, Akimasa Yoshimura, Masafumi Minoshima, Shin Mizukami, Kazuya Kikuchi
Single-molecule imaging (SMI) has been widely utilized to investigate biomolecular dynamics and protein-protein interactions in living cells. However, multicolor SMI of intracellular proteins is challenging because of high background signals and other limitations of current fluorescence labeling approaches. To achieve reproducible intracellular SMI, a labeling probe ensuring both efficient membrane permeability and minimal non-specific binding to cell components is essential. We developed near-infrared (NIR) fluorescent probes for protein-labeling, which specifically binds to a mutant β-lactamase tag...
November 9, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29061850/the-brucella-effector-protein-tcpb-induces-degradation-of-inflammatory-caspases-and-thereby-subverts-noncanonical-inflammasome-activation-in-macrophages
#9
Padmaja Jakka, Swapna Namani, Subathra Murugan, Nivedita Rai, Girish Radhakrishnan
The inflammasome contains intracellular receptors that recognize various pathogen-associated molecular patterns and play crucial roles in innate immune responses to invading pathogens. Noncanonical inflammasome activation is mediated by caspase 4/11, which recognizes intracellular LPS and promotes pyroptosis and secretion of proinflammatory cytokines. Brucella species are infectious intracellular pathogens that replicate in professional and nonprofessional phagocytic cells and subvert immune responses for chronic persistence in the host...
October 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29017773/tlr11-or-tlr12-silencing-reduces-leishmania-major-infection
#10
Divanshu Shukla, Himanshu Singh Chandel, Sunit Srivastava, Prashant Chauhan, Surya Prakash Pandey, Ashok Patidar, Raja Banerjee, Debprasad Chattopadhyay, Bhaskar Saha
Toll-like receptors (TLRs) recognize the pathogen-associated molecular patterns (PAMPs) and induce host-protective immune response. The role of the profilin-recognizing TLR11/TLR12 in Leishmania infection is unknown. Herein, we report that TLR11/ TLR12 expression increases in virulent L. major-infected macrophages but is prevented by miltefosine, an anti-leishmanial drug. While lipohosphoglycan (LPG) increases, LPG or TLR2 blockade prevents, the heightened TLR11/TLR12 expression. LPG-TLR2 interaction triggers MyD88- and TIRAP-mediated signaling enhancing ERK-1/2 activation and increased production of IL-10 that promotes TLR11/TLR12 expression...
October 7, 2017: Cytokine
https://www.readbyqxmd.com/read/28959253/methylation-of-the-vitamin-d-receptor-vdr-gene-together-with-genetic-variation-race-and-environment-influence-the-signaling-efficacy-of-the-toll-like-receptor-2-1-vdr-pathway
#11
Vanessa Meyer, Donovan Sean Saccone, Fidele Tugizimana, Furaha Florence Asani, Tamsyn Jacki Jeffery, Liza Bornman
BACKGROUND: The disparity in prevalence of infectious diseases across the globe is common knowledge. Vitamin D receptor (VDR)-mediated toll-like receptor (TLR) 2/1 signaling produces antimicrobial peptides, which is critical as a first line of defense in innate immunity. Numerous studies disclosed the independent role of genetic polymorphisms in this pathway, vitamin D status or season and more recently epigenetics, as factors contributing to infectious disease predisposition. Few studies address the interaction between environment, genetics, and epigenetics...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28844021/tlr2-tlr3-and-tlr5-regulation-of-pro-inflammatory-and-pro-labour-mediators-in-human-primary-myometrial-cells
#12
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be a significant global health care issue, due to our lack of understanding of the mechanisms that drive human labour and delivery. Toll-like receptors (TLRs) are essential in triggering an inflammatory response in human gestational tissues, leading to the production of pro-inflammatory and pro-labour mediators, and thus preterm birth. The aims of this study were to determine whether the adaptor molecules associated with TLR2, TLR3 and TLR5 signalling are involved in human myometrium...
August 24, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28775078/tlr2-plays-a-key-role-in-platelet-hyperreactivity-and-accelerated-thrombosis-associated-with-hyperlipidemia
#13
Sudipta Biswas, Alejandro Zimman, Detao Gao, Tatiana V Byzova, Eugene A Podrez
RATIONALE: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. OBJECTIVE: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to the accumulation in the circulation of a specific group of oxidized phospholipids (oxPCCD36) that are ligands for the platelet pattern recognition receptor CD36...
September 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28759049/structural-basis-of-tir-domain-assembly-formation-in-mal-and-myd88-dependent-tlr4-signaling
#14
Thomas Ve, Parimala R Vajjhala, Andrew Hedger, Tristan Croll, Frank DiMaio, Shane Horsefield, Xiong Yu, Peter Lavrencic, Zahid Hassan, Garry P Morgan, Ashley Mansell, Mehdi Mobli, Ailis O'Carroll, Brieuc Chauvin, Yann Gambin, Emma Sierecki, Michael J Landsberg, Katryn J Stacey, Edward H Egelman, Bostjan Kobe
Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement...
September 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28739429/llex-paraguariensis-decreases-oxidative-stress-in-bone-and-mitigates-the-damage-in-rats-during-perimenopause
#15
Camila Scacco Pereira, Camila Tami Stringhetta-Garcia, Lilian da Silva Xavier, Keny Gonçalves Tirapeli, Ariana Aparecida Ferreira Pereira, GiselIi Mitsuy Kayahara, José Marcelo Tramarim, Marcelo Macedo Crivelini, Karina Stringhetta Padovani, Andréia Machado Leopoldino, Mário Jefferson Quirino Louzada, Adriane Belló-Klein, Susana Francisca Llesuy, Edilson Ervolino, Rita Cássia Menegati Dornelles, Antonio Hernandes Chaves-Neto, Ana Cláudia de Melo Stevanato Nakamune
During perimenopause, oxidative stress increases, which may result in disruption of bone turnover, and consequently in osteoporosis. The use of antioxidants may be an effective nutritional approach to reducing osteoporosis in this period of life. Mate tea (MT) (Ilex paraguariensis), a typical and inexpensive beverage consumed in the Brazilian south-east, Argentina and Uruguay, increases antioxidant defense. Our hypothesis was that MT would decrease oxidative stress and mitigate bone deterioration. To test this, we analyzed oxidative stress markers of bone turnover, and local and systemic markers of bone metabolism of rats during natural perimenopause...
July 21, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28711717/phosphatidylinositol-4-phosphate-5-kinase-%C3%AE-contributes-to-toll-like-receptor-2-mediated-immune-responses-in-microglial-cells-stimulated-with-lipoteichoic-acid
#16
Tu Thi Ngoc Nguyen, Eunjeong Seo, Juyong Choi, Oanh Thi Tu Le, Ji Yun Kim, Ilo Jou, Sang Yoon Lee
Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important lipid regulator of membrane signaling and remodeling processes. Accumulating evidence indicates a link between PIP2 metabolism and Toll-like receptor (TLR) signaling, a key transducer of immune responses such as inflammation, phagocytosis, and autophagy. Microglia are immune effector cells that serve as macrophages in the brain. Here, we examined the potential role of phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα), a PIP2-producing enzyme, in TLR2 signaling in microglial cells...
July 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28696418/associations-between-functional-polymorphisms-and-response-to-biological-treatment-in-danish-patients-with-psoriasis
#17
N D Loft, L Skov, L Iversen, R Gniadecki, T N Dam, I Brandslund, H J Hoffmann, M R Andersen, R B Dessau, A C Bergmann, N M Andersen, P S Andersen, S Bank, U Vogel, V Andersen
Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28592841/lipopolysaccharides-induced-inflammatory-responses-and-electrophysiological-dysfunctions-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#18
Gökhan Yücel, Zhihan Zhao, Ibrahim El-Battrawy, Huan Lan, Siegfried Lang, Xin Li, Fanis Buljubasic, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Ursula Ravens, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28559111/pattern-recognition-receptors-in-grass-carp-ctenopharyngodon-idella-i-organization-and-expression-analysis-of-tlrs-and-rlrs
#19
Zhiwei Liao, Quanyuan Wan, Hang Su, Changsong Wu, Jianguo Su
Pattern recognition receptors (PRRs) play indispensable roles in the immune responses against invading pathogens. In the present study, we systematically identified and characterized Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) as well as their adaptors in grass carp (Ctenopharyngodon idella). A comprehensive analysis of BLAST and other bioinformatics methods showed that C. idella TLR family consist of 21 members and their adaptors contain four members. Phylogenetic analyses confirmed the existence of six TLR subfamilies (TLR1, 3, 4, 5, 7 and 11 subfamily) in C...
May 27, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28536249/bronchial-inflammation-and-bacterial-load-in-stable-copd-is-associated-with-tlr4-overexpression
#20
Antonino Di Stefano, Fabio L M Ricciardolo, Gaetano Caramori, Ian M Adcock, Kian Fan Chung, Peter J Barnes, Paola Brun, Andrea Leonardi, Filippo Andò, Davide Vallese, Isabella Gnemmi, Luisella Righi, Francesco Cappello, Bruno Balbi
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12)...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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