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https://www.readbyqxmd.com/read/29121163/gene-expression-profiling-reveals-heterogeneity-of-perivascular-adipose-tissues-surrounding-coronary-and-internal-thoracic-arteries
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28528205/heterotrimeric-complex-of-p38-mapk-pkc%C3%AE-and-tirap-is-required-for-ap1-mediated-inflammatory-response
#15
Mirza S Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes...
May 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28483816/a-pseudomonas-aeruginosa%C3%A2-tir-effector-mediates-immune-evasion-by-targeting%C3%A2-ubap1-and-tlr-adaptors
#16
Paul Rc Imbert, Arthur Louche, Jean-Baptiste Luizet, Teddy Grandjean, Sarah Bigot, Thomas E Wood, Stéphanie Gagné, Amandine Blanco, Lydia Wunderley, Laurent Terradot, Philip Woodman, Steve Garvis, Alain Filloux, Benoit Guery, Suzana P Salcedo
Bacterial pathogens often subvert the innate immune system to establish a successful infection. The direct inhibition of downstream components of innate immune pathways is particularly well documented but how bacteria interfere with receptor proximal events is far less well understood. Here, we describe a Toll/interleukin 1 receptor (TIR) domain-containing protein (PumA) of the multi-drug resistant Pseudomonas aeruginosa PA7 strain. We found that PumA is essential for virulence and inhibits NF-κB, a property transferable to non-PumA strain PA14, suggesting no additional factors are needed for PumA function...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28482182/role-of-myd88-adaptor-like-gene-polymorphism-rs8177374-in-modulation-of-malaria-severity-in-the-pakistani-population
#17
Asima Rani, Syed Kashif Nawaz, Shazia Irfan, Muhammad Arshad, Razia Bashir, Najma Shaheen
INTRODUCTION: The present study was designed to investigate the association between rs8177374 polymorphism and malaria symptoms due to exposure of Plasmodium vivax and Plasmodium falciparum. MATERIALS AND METHODS: A total of 454 samples were included in the study (228 malaria patients and 226 healthy individuals). Malaria patients, divided into P. vivax and P. falciparum groups on the basis of the causative species of Plasmodium, were categorized into mild and severe on the basis of clinical outcomes according to WHO criteria...
July 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28330862/when-tlrs-fail-igg-has-your-back
#18
Tiffany C Scharschmidt
Inherited TIRAP deficiency confers susceptibility to staphylococcal disease via impaired TLR2 and TLR4 responses, which can be rescued by bacteria-specific antibodies.
March 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28225045/membrane-targeting-of-tirap-is-negatively-regulated-by-phosphorylation-in-its-phosphoinositide-binding-motif
#19
Xiaolin Zhao, Wen Xiong, Shuyan Xiao, Tuo-Xian Tang, Jeffrey F Ellena, Geoffrey S Armstrong, Carla V Finkielstein, Daniel G S Capelluto
Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28132881/monocyte-lymphocyte-fusion-induced-by-the-hiv-1-envelope-generates-functional-heterokaryons-with-an-activated-monocyte-like-phenotype
#20
David Martínez-Méndez, Evelyn Rivera-Toledo, Enrique Ortega, Ileana Licona-Limón, Leonor Huerta
Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4(+) T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype...
March 1, 2017: Experimental Cell Research
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