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Allan r brasier

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https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#1
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27793799/brd4-mediates-nf%C3%AE%C2%BAb-dependent-epithelial-mesenchymal-transition-and-pulmonary-fibrosis-via-transcriptional-elongation
#2
Bing Tian, Yingxin Zhao, Hong Sun, Yueqing Zhang, Jun Yang, Allan R Brasier
Chronic epithelial injury triggers a TGFβ-mediated cellular transition from normal epithelium into a mesenchymal-like state that produces subepithelial fibrosis and airway remodeling. Here we examined how TGFβ induces the mesenchymal cell state, and determined its mechanism. We observe that TGFβ stimulation activates an inflammatory gene program controlled by the NFκB/RelA signaling pathway. In the mesenchymal state, NFκB-dependent immediate-early genes accumulate euchromatin marks and processive RNA polymerase...
October 28, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27756845/oxidized-guanine-base-lesions-function-in-8-oxoguanine-dna-glycosylase-1-mediated-epigenetic-regulation-of-nuclear-factor-%C3%AE%C2%BAb-driven-gene-expression
#3
Lang Pan, Bing Zhu, Wenjing Hao, Xianlu Zeng, Spiros A Vlahopoulos, Tapas K Hazra, Muralidhar L Hegde, Zsolt Radak, Attila Bacsi, Allan R Brasier, Xueqing Ba, Istvan Boldogh
A large percentage of redox-responsive gene promoters contain evolutionarily conserved guanine-rich clusters; guanines are the bases most susceptible to oxidative modification(s). Consequently, 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the most abundant base lesions in promoters and is primarily repaired via the 8-oxoguanine DNA glycosylase-1 (OOG1)-initiated base excision repair pathway. In view of a prompt cellular response to oxidative challenge, we hypothesized that the 8-oxoG lesion and the cognate repair protein OGG1 are utilized in transcriptional gene activation...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27662828/generation-and-characterization-of-a-novel-transgenic-mouse-harboring-conditional-nuclear-factor-kappa-b-rela-knockout-alleles
#4
Talha Ijaz, Maki Wakamiya, Hong Sun, Adrian Recinos, Ronald G Tilton, Allan R Brasier
BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to-mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of RelA leads to massive apoptosis of liver hepatocytes and death in utero. To study the role of RelA in physiology and in disease states in a manner that circumvents this embryonic lethal phenotype, we have generated a mouse with RelA conditional knockout (CKO) alleles containing loxP sites that are deleted by activated Cre recombinase...
September 23, 2016: BMC Developmental Biology
https://www.readbyqxmd.com/read/27635260/s-nitrosylation-proteome-profile-of-peripheral-blood-mononuclear-cells-in-human-heart-failure
#5
Sue-Jie Koo, Heidi M Spratt, Kizhake V Soman, Susan Stafford, Shivali Gupta, John R Petersen, Maria P Zago, Muge N Kuyumcu-Martinez, Allan R Brasier, John E Wiktorowicz, Nisha Jain Garg
Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls, n = 30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change | ≥1...
2016: International Journal of Proteomics
https://www.readbyqxmd.com/read/27624997/palmitoyl-carnitine-production-by-blood-cells-associates-with-the-concentration-of-circulating-acyl-carnitines-in-healthy-overweight-women
#6
Maria Chondronikola, Rabia Asghar, Xiaojun Zhang, Edgar L Dillon, William J Durham, Zhanpin Wu, Craig Porter, Maria Camacho-Hughes, Yingxin Zhao, Allan R Brasier, Elena Volpi, Melinda Sheffield-Moore, Nicola Abate, Labros Sidossis, Demidmaa Tuvdendorj
BACKGROUND: Circulating acyl-carnitines (acyl-CNTs) are associated with insulin resistance (IR) and type 2 diabetes (T2D) in both rodents and humans. However, the mechanisms whereby circulating acyl-CNTs are increased in these conditions and their role in whole-body metabolism remains unknown. The purpose of this study was to determine if, in humans, blood cells contribute in production of circulating acyl-CNTs and associate with whole-body fat metabolism. METHODS AND RESULTS: Eight non-diabetic healthy women (age: 47 ± 19 y; BMI: 26 ± 1 kg·m(-2)) underwent stable isotope tracer infusion and hyperinsulinemic-euglycemic clamp study to determine in vivo whole-body fatty acid flux and insulin sensitivity...
September 6, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27619163/cytokine-amplification-and-macrophage-effector-functions-in-aortic-inflammation-and-abdominal-aortic-aneurysm-formation
#7
COMMENT
Talha Ijaz, Ronald G Tilton, Allan R Brasier
On April 29, 2015, Son and colleagues published an article entitled "Granulocyte macrophage colony-stimulating factor (GM-CSF) is required for aortic dissection/intramural haematoma" in Nature Communications. The authors observed that the heterozygous Kruppel-like transcription factor 6 (KLF6) deficiency or absence of myeloid-specific KLF6 led to upregulation of macrophage GM-CSF expression, promoted the development of aortic hematoma/dissection, and stimulated abdominal aortic aneurysm (AAA) formation when the vessel wall was subjected to an inflammatory stimulus...
August 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27535058/respiratory-syncytial-virus-infection-triggers-epithelial-hmgb1-release-as-a-damage-associated-molecular-pattern-promoting-a-monocytic-inflammatory-response
#8
Yashoda M Hosakote, Allan R Brasier, Antonella Casola, Roberto P Garofalo, Alexander Kurosky
: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infant and elderly populations worldwide. Currently, there is no efficacious vaccine or therapy available for RSV infection. The molecular mechanisms underlying RSV-induced acute airway disease and associated long-term consequences remain largely unknown; however, experimental evidence suggests that the lung inflammatory response plays a fundamental role in the outcome of RSV infection. High-mobility group box 1 (HMGB1) is a nuclear protein that triggers inflammation when released from activated immune or necrotic cells and drives the pathogenesis of various infectious agents...
November 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27530234/measurement-of-histone-methylation-dynamics-by-one-carbon-metabolic-isotope-labeling-and-high-energy-collisional-dissociation-methylation-signature-ion-detection
#9
Hui Tang, Bing Tian, Allan R Brasier, Lawrence C Sowers, Kangling Zhang
Accumulating evidence suggests that cellular metabolites and nutrition levels control epigenetic modifications, including histone methylation. However, it is not currently possible to measure the metabolic control of histone methylation. Here we report a novel detection method to monitor methyl transfer from serine to histones through the one-carbon metabolic pathway, using stable-isotope labeling and detection of lysine methylation signature ions generated in high-energy-dissociation (HCD) tandem mass spectrometry...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27461979/integrative-proteomic-analysis-reveals-reprograming-tumor-necrosis-factor-signaling-in-epithelial-mesenchymal-transition
#10
Yingxin Zhao, Bing Tian, Rovshan G Sadygov, Yueqing Zhang, Allan R Brasier
UNLABELLED: The airway epithelium is a semi-impermeable barrier whose disruption by growth factor reprogramming is associated with chronic airway diseases of humans. Transforming growth factor beta (TGFβ)-induced epithelial mesenchymal transition (EMT) plays important roles in airway remodeling characteristic of idiopathic lung fibrosis, asthma and chronic obstructive pulmonary disease (COPD). Inflammation of the airways leads to airway injury and tumor necrosis factor alpha (TNFα) plays an important pro-inflammatory role...
October 4, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27239029/dysregulation-of-rbfox2-is-an-early-event-in-cardiac-pathogenesis-of-diabetes
#11
Curtis A Nutter, Elizabeth A Jaworski, Sunil K Verma, Vaibhav Deshmukh, Qiongling Wang, Olga B Botvinnik, Mario J Lozano, Ismail J Abass, Talha Ijaz, Allan R Brasier, Nisha J Garg, Xander H T Wehrens, Gene W Yeo, Muge N Kuyumcu-Martinez
Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 controls AS of genes with important roles in heart function relevant to diabetic cardiomyopathy. RBFOX2 protein levels are elevated in diabetic hearts despite low RBFOX2 AS activity. A dominant-negative (DN) isoform of RBFOX2 that blocks RBFOX2-mediated AS is generated in diabetic hearts...
June 7, 2016: Cell Reports
https://www.readbyqxmd.com/read/26919708/changes-in-proteome-profile-of-peripheral-blood-mononuclear-cells-in-chronic-chagas-disease
#12
Nisha Jain Garg, Kizhake V Soman, Maria P Zago, Sue-Jie Koo, Heidi Spratt, Susan Stafford, Zinzi N Blell, Shivali Gupta, Julio Nuñez Burgos, Natalia Barrientos, Allan R Brasier, John E Wiktorowicz
Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy controls (N/H, n = 30) and subjects that were seropositive for Tc-specific antibodies, but were clinically asymptomatic (C/A, n = 25) or clinically symptomatic (C/S, n = 28) with cardiac involvement and left ventricular dysfunction...
February 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/26586036/myeloid-differentiation-protein-2-facilitates-pollen-and-cat-dander-induced-innate-and-allergic-airway-inflammation
#13
Koa Hosoki, Istvan Boldogh, Leopoldo Aguilera-Aguirre, Qian Sun, Toshiko Itazawa, Tapas Hazra, Allan R Brasier, Alexander Kurosky, Sanjiv Sur
BACKGROUND: The National Health and Nutrition Examination Survey identified several pollens and cat dander as among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein 2 (MD2) is a TLR4 coreceptor, but its role in pollen- and cat dander-induced innate and allergic inflammation has not been critically evaluated...
May 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26581097/improved-detection-of-invasive-pulmonary-aspergillosis-arising-during-leukemia-treatment-using-a-panel-of-host-response-proteins-and-fungal-antigens
#14
Allan R Brasier, Yingxin Zhao, Heidi M Spratt, John E Wiktorowicz, Hyunsu Ju, L Joseph Wheat, Lindsey Baden, Susan Stafford, Zheng Wu, Nicolas Issa, Angela M Caliendo, David W Denning, Kizhake Soman, Cornelius J Clancy, M Hong Nguyen, Michele W Sugrue, Barbara D Alexander, John R Wingard
Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial...
2015: PloS One
https://www.readbyqxmd.com/read/26560068/endothelial-cell-proteomic-response-to-rickettsia-conorii-infection-reveals-activation-of-the-janus-kinase-jak-signal-transducer-and-activator-of-transcription-stat-inferferon-stimulated-gene-isg-15-pathway-and-reprogramming-plasma-membrane-integrin-cadherin
#15
Yingxin Zhao, Gustavo Valbuena, David H Walker, Michal Gazi, Marylin Hidalgo, Rita DeSousa, Jose Antonio Oteo, Yenny Goez, Allan R Brasier
Rickettsia conorii is the etiologic agent of Mediterranean spotted fever, a re-emerging infectious disease with significant mortality. This Gram-negative, obligately intracellular pathogen is transmitted via tick bites, resulting in disseminated vascular endothelial cell infection with vascular leakage. In the infected human, Rickettsia conorii infects endothelial cells, stimulating expression of cytokines and pro-coagulant factors. However, the integrated proteomic response of human endothelial cells to R...
January 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/26209609/systematic-determination-of-human-cyclin-dependent-kinase-cdk-9-interactome-identifies-novel-functions-in-rna-splicing-mediated-by-the-dead-box-ddx-5-17-rna-helicases
#16
Jun Yang, Yingxin Zhao, Mridul Kalita, Xueling Li, Mohammad Jamaluddin, Bing Tian, Chukwudi B Edeh, John E Wiktorowicz, Andrzej Kudlicki, Allan R Brasier
Inducible transcriptional elongation is a rapid, stereotypic mechanism for activating immediate early immune defense genes by the epithelium in response to viral pathogens. Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with innate immune response (IIR) genes. To identify additional functional activity of the CDK9 complex, we conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of the CDK9 complex in unstimulated cells and from cells activated by a synthetic dsRNA, polyinosinic/polycytidylic acid [poly (I:C)]...
October 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/26187872/whole-transcriptome-analysis-reveals-a-role-for-ogg1-initiated-dna-repair-signaling-in-airway-remodeling
#17
Leopoldo Aguilera-Aguirre, Koa Hosoki, Attila Bacsi, Zsolt Radák, Sanjiv Sur, Muralidhar L Hegde, Bing Tian, Alfredo Saavedra-Molina, Allan R Brasier, Xueqing Ba, Istvan Boldogh
Reactive oxygen species (ROS) generated by environmental exposures, and endogenously as by-products of respiration, oxidatively modify biomolecules including DNA. Accumulation of ROS-induced DNA damage has been implicated in various diseases that involve inflammatory processes, and efficient DNA repair is considered critical in preventing such diseases. One of the most abundant DNA base lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which is repaired by the 8-oxoguanine DNA glycosylase 1 (OGG1)-initiated base-excision repair (OGG1-BER) pathway...
December 2015: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26187636/analysis-of-the-tgf%C3%AE-induced-program-in-primary-airway-epithelial-cells-shows-essential-role-of-nf-%C3%AE%C2%BAb-rela-signaling-network-in-type-ii-epithelial-mesenchymal-transition
#18
Bing Tian, Xueling Li, Mridul Kalita, Steven G Widen, Jun Yang, Suresh K Bhavnani, Bryant Dang, Andrzej Kudlicki, Mala Sinha, Fanping Kong, Thomas G Wood, Bruce A Luxon, Allan R Brasier
BACKGROUND: The airway epithelial cell plays a central role in coordinating the pulmonary response to injury and inflammation. Here, transforming growth factor-β (TGFβ) activates gene expression programs to induce stem cell-like properties, inhibit expression of differentiated epithelial adhesion proteins and express mesenchymal contractile proteins. This process is known as epithelial mesenchymal transition (EMT); although much is known about the role of EMT in cellular metastasis in an oncogene-transformed cell, less is known about Type II EMT, that occurring in normal epithelial cells...
2015: BMC Genomics
https://www.readbyqxmd.com/read/26086549/facilitation-of-allergic-sensitization-and-allergic-airway-inflammation-by-pollen-induced-innate-neutrophil-recruitment
#19
Koa Hosoki, Leopoldo Aguilera-Aguirre, Allan R Brasier, Alexander Kurosky, Istvan Boldogh, Sanjiv Sur
Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways...
January 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/26073125/respiratory-syncytial-virus-infection-down-regulates-antioxidant-enzyme-expression-by-triggering-deacetylation-proteasomal-degradation-of-nrf2
#20
Narayana Komaravelli, Bing Tian, Teodora Ivanciuc, Nicholas Mautemps, Allan R Brasier, Roberto P Garofalo, Antonella Casola
Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or treatment is available. RSV infection in cells, mice, and children leads to rapid generation of reactive oxygen species, which are associated with oxidative stress and lung damage, due to a significant decrease in the expression of airway antioxidant enzymes (AOEs). Oxidative stress plays an important role in the pathogenesis of RSV-induced lung disease, as antioxidants ameliorate clinical disease and inflammation in vivo...
November 2015: Free Radical Biology & Medicine
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