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https://www.readbyqxmd.com/read/28592841/lipopolysaccharides-induced-inflammatory-responses-and-electrophysiological-dysfunctions-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#1
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
#2
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
#3
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
#4
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
#5
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...
May 8, 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
#6
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...
May 6, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28330862/when-tlrs-fail-igg-has-your-back
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28115213/two-novel-candidate-genes-identified-in-adults-from-the-newfoundland-population-with-addictive-tendencies-towards-food
#10
Pardis Pedram, Guangju Zhai, Wayne Gulliver, Hongwei Zhang, Guang Sun
Food addiction (FA) is a distinguished clinical feature affecting about 5% adults of the general population in Canada. FA contributes to obesity, however, the underlying genes in FA are largely unknown. The aim of the current study was to search for FA candidate genes using an exome sequencing followed by a verification study using the most significantly associated identified genes. From a total of 752 adults, 24 subjects were selected including 8 obese with high and 8 obese with low/zero FA clinical symptom score (FAO, NFO), and 8 healthy controls with normal BMI and low/zero FA symptom score (Ctrl)...
August 1, 2017: Appetite
https://www.readbyqxmd.com/read/28095310/ilex-paraguariensis-supplementation-may-be-an-effective-nutritional-approach-to-modulate-oxidative-stress-during-perimenopause
#11
Ariana Aparecida Ferreira Pereira, Keny Gonçalves Tirapeli, Antonio Hernandes Chaves-Neto, Matheus da Silva Brasilino, Cláudia Quintino da Rocha, Adriane Belló-Klein, Suzana Francisca Llesuy, Rita Cássia Menegati Dornelles, Ana Cláudia de Melo Stevanato Nakamune
Perimenopause is a period in a woman's life that precedes menopause and is characterized by hormonal changes that result in increased oxidative stress. Since oxidative stress is associated with age-related diseases and perimenopausal symptoms including somato-vegetative manifestations, nutritional antioxidant supplementation may be an effective approach to minimizing this stress. Mate tea (MT) (Ilex paraguariensis), a typical and inexpensive beverage consumed in the Brazilian south-east, Argentina and Uruguay, increases antioxidant defense...
April 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/27909057/structure-of-the-toll-interleukin-1-receptor-tir-domain-of-the-b-cell-adaptor-that-links-phosphoinositide-metabolism-with-the-negative-regulation-of-the-toll-like-receptor-tlr-signalosome
#12
Samer Halabi, Eiki Sekine, Brett Verstak, Nicholas J Gay, Martin C Moncrieffe
Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic Toll/interleukin-1 receptor (TIR) domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors and pro-inflammatory molecules and the activation of phosphoinositide 3-kinases (PI3K) in a process that requires the multimodular B-cell adaptor for phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902980/gene-expression-profiling-and-functional-characterization-of-macrophages-in-response-to-circulatory-microparticles-produced-during-trypanosoma-cruzi-infection-and-chagas-disease
#13
Imran H Chowdhury, Sue-Jie Koo, Shivali Gupta, Lisa Yi Liang, Bojlul Bahar, Laura Silla, Julio Nuñez-Burgos, Natalia Barrientos, Maria Paola Zago, Nisha Jain Garg
BACKGROUND: Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHODS: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs...
2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27811020/impact-of-ctla4-genotype-and-other-immune-response-gene-polymorphisms-on-outcomes-after-single-umbilical-cord-blood-transplantation
#14
Renato Cunha, Marco A Zago, Sergio Querol, Fernanda Volt, Annalisa Ruggeri, Guillermo Sanz, Fabienne Pouthier, Gesine Kogler, José L Vicario, Paola Bergamaschi, Riccardo Saccardi, Carmen H Lamas, Cristina Díaz-de-Heredia, Gerard Michel, Henrique Bittencourt, Marli Tavella, Rodrigo A Panepucci, Francisco Fernandes, Julia Pavan, Eliane Gluckman, Vanderson Rocha
We evaluated the impact of recipient and cord blood unit (CBU) genetic polymorphisms related to immune response on outcomes after unrelated cord blood transplantations (CBTs). Pretransplant DNA samples from 696 CBUs with malignant diseases were genotyped for NLRP1, NLRP2, NLRP3, TIRAP/Mal, IL10, REL, TNFRSF1B, and CTLA4. HLA compatibility was 6 of 6 in 10%, 5 of 6 in 39%, and ≥4 of 6 in 51% of transplants. Myeloablative conditioning was used in 80%, and in vivo T-cell depletion in 81%, of cases. The median number of total nucleated cells infused was 3...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/27646001/myd88-adapter-like-mal-tirap-is-required-for-cytokine-production-by-splenic-ly6clotlr2hi-but-not-by-ly6chitlr2hi-monocytes-during-trypanosoma-cruzi-infection
#15
Humberto Doriguêtto Gravina, Alfredo Miranda Goes, Silvane Maria Fonseca Murta, Catherine Ropert
This study continues to explore the plasticity of Toll-like receptor 2 (TLR2) previously described in immune response during Trypanosoma cruzi infection. Here, we have shown that Ly6C(hi)TLR2(hi) monocytes were involved in TNF-α and IL-12 production, whereas Ly6C(lo)TLR2(hi) monocytes were mainly committed to IL-10 and TNF-α production during T. cruzi infection independently of TLR agonist used (i.e. TLR2 or TLR9 agonists). Another difference between the monocyte populations is that the adapter Mal (encoded by TIRAP) has appeared crucial for the cytokine production by Ly6C(lo) but not by Ly6C(hi) monocytes...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27457283/association-of-tlr-polymorphisms-with-bronchopulmonary-dysplasia
#16
Amr Hosny Malash, Aliaa Adel Ali, Rania Mohamed Samy, Radwa Ahmed Shamma
Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity and mortality during infancy. Evidence suggests that the Toll-like receptor (TLR) signaling pathway plays an integral role in lung inflammation and injury. This study aimed to detect single nucleotide polymorphisms (SNPs) in TLR pathway genes [TLR5 and Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP)] among preterm neonates and to determine their association with the development and severity of bronchopulmonary dysplasia...
October 30, 2016: Gene
https://www.readbyqxmd.com/read/27431585/comparative-genomic-evidence-for-duplication-of-tlr1-subfamily-and-miiuy-croaker-tlr1-perceives-lps-stimulation-via-myd88-and-tirap
#17
Tianjun Xu, Yanjin Wang, Jinrui Li, Chang Shu, Jingjing Han, Qing Chu
Being indispensable pattern recognition receptors in innate immune responses in host protection, Toll-like receptors (TLRs) play an important role in pathogen recognition. Fish TLRs exhibit high variety and distinct features, although little is known about their function on ligand recognition and signaling pathway in fish. This paper reports the evolutionary spectrum of the TLR1 subfamily (referred to as TLR1, TLR6, and TLR10) as determined using the comparative genomic approach. We hypothesized that the TLR1 subfamily underwent two rounds of gene duplication events; the first duplication occurred prior to the divergence of amphibians, and the second one occurred prior to the divergence of eutherians...
September 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27311859/brucella-tir-like-protein-tcpb-btp1-specifically-targets-the-host-adaptor-protein-mal-tirap-to-promote-infection
#18
Wenna Li, Yuehua Ke, Yufei Wang, Mingjuan Yang, Junguang Gao, Shaoxia Zhan, Du Xinying, Liuyu Huang, Wenfeng Li, Zeliang Chen, Juan Li
Brucella spp. are known to avoid host immune recognition and weaken the immune response to infection. Brucella like accomplish this by employing two clever strategies, called the stealth strategy and hijacking strategy. The TIR domain-containing protein (TcpB/Btp1) of Brucella melitensis is thought to be involved in inhibiting host NF-κB activation by binding to adaptors downstream of Toll-like receptors. However, of the five TIR domain-containing adaptors conserved in mammals, whether MyD88 or MAL, even other three adaptors, are specifically targeted by TcpB has not been identified...
August 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27256462/defects-in-early-cell-recruitment-contribute-to-the-increased-susceptibility-to-respiratory-klebsiella-pneumoniae-infection-in-diabetic-mice
#19
Nuria Martinez, Natkunam Ketheesan, Gregory W Martens, Kim West, Egil Lien, Hardy Kornfeld
Diabetes is associated with increased susceptibility to Klebsiella pneumoniae and poor prognosis with infection. We demonstrate accelerated mortality in mice with streptozotocin-induced diabetes following tracheal instillation of K. pneumoniae. Diabetic mice recruited fewer granulocytes to the alveolar airspace and had reduced early production of CXCL1, CXCL2, IL-1β and TNF-α following tracheal instillation of K. pneumoniae-lipopolysaccharide. Additionally, TLR2 and TIRAP expression following K. pneumoniae-lipopolysaccharide exposure was decreased in hyperglycemic mice...
October 2016: Microbes and Infection
https://www.readbyqxmd.com/read/27214039/tlr1-variant-h305l-associated-with-protection-from-pulmonary-tuberculosis
#20
Christian G Meyer, Norbert Reiling, Christa Ehmen, Gerd Ruge, Ellis Owusu-Dabo, Rolf D Horstmann, Thorsten Thye
Toll like receptors (TLR) are key elements of the innate immune response and involved in the recognition of pathogens. To test common and rare TLR variants involved in susceptibility or resistance to infection with Mycobacterium tuberculosis we screened the exons of the genes encoding TLR 1, 2, 4, and the adaptor molecule TIRAP in more than 4500 tuberculosis (TB) cases and controls from Ghana. The analysis yielded 109 variants with possible functional impact, including 101 non-synonymous variants, three stop-variants, and five indels...
2016: PloS One
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