DOCSLIB.ORG

Leukocyte Attraction Macrophages with Distinct Changes in Adaptive

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Leukocyte Attraction Macrophages with Distinct Changes in Adaptive Chronic Exposure to Glucocorticoids Shapes Gene Expression and Modulates Innate and Adaptive Activation Pathways in Macrophages with Distinct Changes in This information is current as Leukocyte Attraction of September 26, 2021. Martijn D. B. van de Garde, Fernando O. Martinez, Barbro N. Melgert, Machteld N. Hylkema, René E. Jonkers and Jörg Hamann J Immunol 2014; 192:1196-1208; Prepublished online 6 Downloaded from January 2014; doi: 10.4049/jimmunol.1302138 http://www.jimmunol.org/content/192/3/1196 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2014/01/05/jimmunol.130213 Material 8.DCSupplemental References This article cites 56 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/192/3/1196.full#ref-list-1 by guest on September 26, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Chronic Exposure to Glucocorticoids Shapes Gene Expression and Modulates Innate and Adaptive Activation Pathways in Macrophages with Distinct Changes in Leukocyte Attraction Martijn D. B. van de Garde,*,1 Fernando O. Martinez,†,1 Barbro N. Melgert,‡,x || Machteld N. Hylkema,x,{ Rene´ E. Jonkers, and Jo¨rg Hamann* Glucocorticoids (GCs) have been used for more than 50 y as immunosuppressive drugs, yet their efficacy in macrophage-dominated disorders, such as chronic obstructive pulmonary disease, is debated. Little is known how long-term GC treatment affects macrophage responses in inflammatory conditions. In this study, we compared the transcriptome of human macrophages, matured in the presence or absence of fluticasone propionate (FP), and their ability to initiate or sustain classical activation, mimicked using acute LPS and chronic IFN-g stimulation, respectively. We identified macrophage gene expression networks, modulated by FP long-term exposure, Downloaded from and specific patterns of IFN-g– and LPS-induced genes that were resistant, inhibited, or exacerbated by FP. Results suggest that long-term treatment with GCs weakens adaptive immune signature components of IFN-g and LPS gene profiles by downmodulating MHC class II and costimulatory molecules, but strengthens innate signature components by maintaining and increasing expression of chemokines involved in phagocyte attraction. In a mouse model of chronic obstructive pulmonary disease, GC treatment induced higher chemokine levels, and this correlated with enhanced recruitment of leukocytes. Thus, GCs do not generally suppress macrophage effector functions, but they cause a shift in the innate–adaptive balance of the immune response, with distinct changes http://www.jimmunol.org/ in the chemokine–chemokine receptor network. The Journal of Immunology, 2014, 192: 1196–1208. acrophages are innate immune cells with well-established of a developing concept: macrophage plasticity (3). Plasticity is roles in tissue homeostasis, primary response to patho- naturally the basis of macrophage heterogeneity in basal and M gens, coordination of adaptive immunity, and even wound inflammatory conditions; it is also the basis of worldwide efforts repair (1, 2). Macrophages accomplish these varied roles by adapting to treat diseases by subverting aberrant macrophage activation. their gene and protein expression programs in response to endoge- Macrophage-mediated inflammation is increasingly recognized nous and exogenous environmental cues, such as cytokines and as contributing to chronic inflammatory disorders, such as chronic pathogen-associated molecular patterns. The ability of macrophages obstructive pulmonary disease (COPD), severe asthma, rheumatoid by guest on September 26, 2021 to change their gene and protein signatures falls under the umbrella arthritis, and multiple sclerosis (4). The best-characterized macrophage activation pathway has been called classical macrophage activation, and it is triggered by *Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; †Sir William Dunn School of the recognition of pathogen-associated molecular patterns by TLRs, Pathology and Kennedy Institute of Rheumatology, University of Oxford, Oxford supported by further elicitation of IFN pathways (2). Classically ‡ OX1 3RE, United Kingdom; Department of Pharmacokinetics, Toxicology and activated macrophages produce microbicidal enzymes, such as Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands; xGroningen Research Institute for Asthma inducible NO synthase, inflammatory cytokines, such as TNF, IL-6, and COPD, University Medical Center Groningen, University of Groningen, IL-1b,IL-12,andIFN-b, various chemoattractants, and matrix 9713 GZ Groningen, The Netherlands; {Department of Pathology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The metallopeptidases (MMPs). These mediators support IFN-g–mediated Netherlands; and ||Department of Pulmonology, Academic Medical Center, University Th1 responses, which are important for sustained antimicrobial of Amsterdam, 1105 AZ Amsterdam, The Netherlands activity but are deleterious in chronic diseases, because they lead to 1 M.D.B.v.d.G. and F.O.M. contributed equally to this work. tissue damage and chronic inflammation. Received for publication August 14, 2013. Accepted for publication November 25, To limit macrophage activation and restore homeostasis, endog- 2013. enous glucocorticoids (GCs) induce anti-inflammatory programs via This work was supported by a grant from the J.K. de Cock Stichting and Prof. Dirkje Postma through a Spinoza grant from the Dutch Government. the GC receptor (GCR) (5, 6). GCR agonists are prescribed for a wide range of inflammatory disorders, and their use is crucial to Address correspondence and reprint requests to Dr. Fernando O. Martinez or Dr. Jo¨rg Hamann, Kennedy Rheumatology Institute, Nuffield Department of Orthopaedics, treat diseases of the respiratory tract, especially asthma (6). Drugs Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University such as prednisolone, dexamethasone, budesonide, and fluticasone of Oxford, Windmill Road, Headington, Oxford, OX37 LD, U.K. (F.O.M.) or De- partment of Experimental Immunology, Academic Medical Center, University of propionate (FP) share great GCR specificity albeit different phar- Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (J.H.). E-mail macodynamics (7). The remarkable efficacy of GCs in suppressing addresses: [email protected] (F.O.M.) or j.hamann@amc. uva.nl (J.H.) inflammation and decreasing lymphocyte activation, proliferation, The online version of this article contains supplemental material. and survival is well appreciated. However, our knowledge of the interactions of GC and inflammatory pathways in human mac- Abbreviations used in this article: COPD, chronic obstructive pulmonary disease; FP, fluticasone propionate; GC, glucocorticoid; GCR, GC receptor; IPA, Ingenuity Path- rophages remains limited (8), and recent studies have shown that GCs ways Analysis; MDM, monocyte-derived macrophage; MEV, Multiple Experiment may have little effect in controlling inflammation in macrophage- Viewer; MMP, matrix metalloproteinase. dominated diseases, and their long-term use is associated with Copyright Ó 2014 by The American Association of Immunologists, Inc. 0022-1767/14/$16.00 persisting complications (9–16). www.jimmunol.org/cgi/doi/10.4049/jimmunol.1302138 The Journal of Immunology 1197 In this study, we investigated from a whole genome point of view study we focused our analysis on data generated on human cells backed the effects of chronic GCR ligation on the maturation of human up by experimental evidence. Data compliant for Minimum Information macrophages and on their ability to initiate and sustain classical About a Microarray Experiment for the datasets used in this study are deposited in Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo/) pro- activation that is important for Th1 inflammation, dissected by files dataset GSE49852. This dataset is part of a superseries—GSE35495— acute and chronic stimulation with the TLR4 ligand LPS and IFN-g. that covers microarrays over the spectrum of macrophage activation, in- We show that long-term treatment with FP modulates classical cluding IFN-g, IL-4, IL-10, IL-13, and dexamethasone (18). activation in human inflammatory macrophage models in a com- For comparison, CEL files generated by Ehrchen et al. (19) in a microarray analysis of monocytes stimulated with FP for 16 h were summarized as plex and not solely suppressive manner by maintaining or even Robust Multiarray Averaging, and quantiles were normalized using Affy increasing the expression of chemokines
Load more

Recommended publications
  • Compression of Large Sets of Sequence Data Reveals Fine Diversification of Functional Profiles in Multigene Families of Proteins
    Technical note Compression of Large Sets of Sequence Data Reveals Fine Diversification of Functional Profiles in Multigene Families of Proteins: A Study for Peptidyl-Prolyl cis/trans Isomerases (PPIase) Andrzej Galat Retired from: Service d’Ingénierie Moléculaire des Protéines (SIMOPRO), CEA-Université Paris-Saclay, France; [email protected]; Tel.: +33-0164465072 Received: 21 December 2018; Accepted: 21 January 2019; Published: 11 February 2019 Abstract: In this technical note, we describe analyses of more than 15,000 sequences of FK506- binding proteins (FKBP) and cyclophilins, also known as peptidyl-prolyl cis/trans isomerases (PPIases). We have developed a novel way of displaying relative changes of amino acid (AA)- residues at a given sequence position by using heat-maps. This type of representation allows simultaneous estimation of conservation level in a given sequence position in the entire group of functionally-related paralogues (multigene family of proteins). We have also proposed that at least two FKBPs, namely FKBP36, encoded by the Fkbp6 gene and FKBP51, encoded by the Fkbp5 gene, can form dimers bound via a disulfide bridge in the nucleus. This type of dimer may have some crucial function in the regulation of some nuclear complexes at different stages of the cell cycle. Keywords: FKBP; cyclophilin; PPIase; heat-map; immunophilin 1 Introduction About 30 years ago, an exciting adventure began in finding some correlations between pharmacological activities of macrocyclic hydrophobic drugs, namely the cyclic peptide cyclosporine A (CsA), and two macrolides, namely FK506 and rapamycin, which have profound and clinically useful immunosuppressive effects, especially in organ transplantations and in combating some immune disorders.
    [Show full text]
  • DNA Methylation of FKBP5 in South African Women: Associations with Obesity and Insulin Resistance Tarryn Willmer1,2* , Julia H
    Willmer et al. Clinical Epigenetics (2020) 12:141 https://doi.org/10.1186/s13148-020-00932-3 RESEARCH Open Access DNA methylation of FKBP5 in South African women: associations with obesity and insulin resistance Tarryn Willmer1,2* , Julia H. Goedecke3,4, Stephanie Dias1, Johan Louw1,5 and Carmen Pheiffer1,2 Abstract Background: Disruption of the hypothalamic–pituitary–adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis. Methods: Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman’s correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction. Results: Two CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots.
    [Show full text]
  • Impact of Fkbp5 × Early Life Adversity × Sex in Humanized Mice on Multidimen- Sional Stress Responses and Circadian Rhythmicity
    bioRxiv preprint doi: https://doi.org/10.1101/2021.07.06.450863; this version posted July 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Title Page Title Impact of Fkbp5 × Early Life Adversity × Sex in Humanized Mice on Multidimen- sional Stress Responses and Circadian Rhythmicity Corresponding Author M.Sc. Verena Nold Boehringer Ingelheim Pharma GmbH & Co KG, CNSDR (and Ulm University, Clinical & Biological Psychology) Birkendorferstraße 65 88397 Biberach an der Riß Germany [email protected] https://orcid.org/0000-0003-0302-0966 Phone +49 (7351) 54-187968 Co-Authors Michelle Portenhauser, Boehringer Ingelheim Pharma GmbH & Co KG Dr. Dolores Del Prete, BioMedX Institute, Heidelberg Andrea Blasius, Boehringer Ingelheim Pharma GmbH & Co KG Isabella Harris, University of Manchester, England Dr. Eliza Koros, Boehringer Ingelheim Pharma GmbH & Co KG Dr. Tatiana Peleh, Boehringer Ingelheim Pharma GmbH & Co KG Prof. Dr. Bastian Hengerer, Boehringer Ingelheim Pharma GmbH & Co KG Prof. Dr. Iris-Tatjana Kolassa, Ulm University, Clinical & Biological Psychology Dr. Michal Slezak,Lukasiewicz Research Network - Polish Center for Technology Development Dr. Kelly Ann Allers, Boehringer Ingelheim Pharma GmbH & Co KG Running Title Early Life Adversity × Fkbp5 Polymorphisms Modulate Adult Stress Physiology Keywords Fkbp5, early life adversity, stress resilience, psychiatric disorder, animal model, cir- cadian rhythmicity 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.06.450863; this version posted July 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Interaction of Polymorphisms in the Fkbp5 Gene & Childhood Adversity on the Cortisol Response to a Psychosocial Stress Task in Adolescents and Young Adults
    INTERACTION OF POLYMORPHISMS IN THE FKBP5 GENE & CHILDHOOD ADVERSITY ON THE CORTISOL RESPONSE TO A PSYCHOSOCIAL STRESS TASK IN ADOLESCENTS AND YOUNG ADULTS by Raegan Mazurka A thesis submitted to the Department of Psychology In conformity with the requirements for the degree of Master of Science Queen’s University Kingston, Ontario, Canada (September, 2013) Copyright © Raegan Mazurka, 2013 Abstract Childhood adversity is often associated with devastating physical, cognitive, and psychosocial outcomes, and is a major public health problem in terms of its prevalence and economic cost. Childhood adversity is associated with increased risk for psychopathology, as well as with dysregulation of the neurobiological stress response. An additional factor known to alter neuroendocrine functioning and increase psychopathology risk is polymorphisms within the FKBP5 gene. The goal of the current study was to examine the gene-environment interaction of childhood adversity and variation in the FKBP5 gene on the cortisol response to a psychosocial stress task (i.e., the Trier Social Stress Test). The final sample consisted of 90 depressed and non- depressed adolescents and young adults (11 - 21 years). Childhood adversity was assessed using the Childhood Experience and Abuse Scale (CECA; Bifulco et al., 1994), and was defined as the presence versus absence prior to 18 years of age of severe physical, sexual, or emotional abuse or neglect, witness to domestic discord/violence, or peer-perpetrated bullying. Participants were genotyped at the rs1360780 site of the FKBP5 gene and grouped according to whether they had at least one risk T allele (i.e., TT or TC genotype versus the CC genotype).
    [Show full text]
  • Roadmap for Resilience: the California Surgeon General's
    DECEMBER 09, 2020 Roadmap for Resilience The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health Suggested citation for the report: Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812. OFFICE OF THE GOVERNOR December 2, 2020 In one of my first acts as Governor, I established the role of California Surgeon General. Among all the myriad challenges facing our administration on the first day, addressing persistent challenges to the health and welfare of the people of our state—especially that of the youngest Californians—was an essential priority. We led with the overwhelming scientific consensus that upstream factors, including toxic stress and the social determinants of health, are the root causes of many of the most harmful and persistent health challenges, from heart disease to homelessness. An issue so critical to the health of 40 million Californians deserved nothing less than a world-renowned expert and advocate. Appointed in 2019 to be the first- ever California Surgeon General, Dr. Nadine Burke Harris brought groundbreaking research and expertise in childhood trauma and adversity to the State’s efforts. In this new role, Dr. Burke Harris set three key priorities – early childhood, health equity and Adverse Childhood Experiences (ACEs) and toxic stress – and is working across my administration to give voice to the science and evidence-based practices that are foundational to the success of our work as a state.
    [Show full text]
  • The Impact of the FKBP5 Gene Polymorphisms on the Relationship Between Traumatic Life Events and Psychotic-Like Experiences in Non-Clinical Adults
    brain sciences Article The Impact of the FKBP5 Gene Polymorphisms on the Relationship between Traumatic Life Events and Psychotic-Like Experiences in Non-Clinical Adults Filip Stramecki 1 , Dorota Frydecka 1, Łukasz Gaw˛eda 2, Katarzyna Prochwicz 3, Joanna Kłosowska 3 , Jerzy Samochowiec 4 , Krzysztof Szczygieł 4, Edyta Pawlak 5 , Elzbieta˙ Szmida 6 , Paweł Skiba 6, Andrzej Cechnicki 7 and Błazej˙ Misiak 1,* 1 Department of Psychiatry, Wroclaw Medical University, Pasteur Street 10, 50-367 Wroclaw, Poland; [email protected] (F.S.); [email protected] (D.F.) 2 Clinical Neuroscience Lab, Institute of Psychology, Polish Academy of Sciences, Jaracza Street 1, 00-378 Warsaw, Poland; [email protected] 3 Institute of Psychology, Jagiellonian University, Ingardena 6 Street, 30-060 Krakow, Poland; [email protected] (K.P.); [email protected] (J.K.) 4 Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26 Street, 71-457 Szczecin, Poland; [email protected] (J.S.); [email protected] (K.S.) 5 Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla Street 12, 53-114 Wroclaw, Poland; [email protected] 6 Citation: Stramecki, F.; Frydecka, D.; Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1 Street, 50-368 Wroclaw, Poland; [email protected] (E.S.); [email protected] (P.S.) Gaw˛eda,Ł.; Prochwicz, K.; 7 Department of Community Psychiatry, Medical College Jagiellonian University, Sikorskiego Place 2, Kłosowska, J.; Samochowiec, J.; 31-115 Krakow, Poland; [email protected] Szczygieł, K.; Pawlak, E.; Szmida, E.; * Correspondence: [email protected] Skiba, P.; et al.
    [Show full text]
  • Altered Metabotropic Glutamate Receptor 5 Markers in PTSD: in Vivo and Postmortem Evidence,” by Sophie E
    Correction NEUROSCIENCE Correction for “Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence,” by Sophie E. Holmes, Matthew J. Girgenti, Margaret T. Davis, Robert H. Pietrzak, Nicole DellaGioia, Nabeel Nabulsi, David Matuskey, Steven Southwick, Ronald S. Duman, Richard E. Carson, John H. Krystal, Irina Esterlis, and the Traumatic Stress Brain Study Group, which was first pub- lished July 17, 2017; 10.1073/pnas.1701749114 (Proc Natl Acad Sci USA 114:8390–8395). The authors note that the affiliation for c should instead appear as National Center for PTSD, Clinical Neurosciences Division, West Haven, CT 06516. The authors also note that this affiliation should be applied to Steven Southwick, in addition to affiliations a and b. The corrected author and affiliation lines appear below. The online version has been corrected. Sophie E. Holmesa,b, Matthew J. Girgentia,b,c,MargaretT. Davisa,b, Robert H. Pietrzaka,b,c, Nicole DellaGioiaa,b, Nabeel Nabulsia,b, David Matuskeya,b, Steven Southwicka,b,c, Ronald S. Dumana,b,c, Richard E. Carsona,b, John H. Krystala,b,c, Irina Esterlisa,b,c, and the Traumatic Stress Brain Study Group aDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT 06519; bDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06519; and cNational Center for PTSD, Clinical Neurosciences Division, West Haven, CT 06516 www.pnas.org/cgi/doi/10.1073/pnas.1714425114 E7852 | PNAS | September 12, 2017 | vol. 114 | no. 37 www.pnas.org Downloaded by guest on September 29, 2021 Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence Sophie E.
    [Show full text]
  • Identifying the Proteins to Which Small-Molecule Probes and Drugs Bind in Cells
    Identifying the proteins to which small-molecule probes and drugs bind in cells Shao-En Onga,1, Monica Schenonea, Adam A. Margolinb, Xiaoyu Lic, Kathy Doa, Mary K. Doudd, D. R. Mania,b, Letian Kuaie, Xiang Wangd, John L. Woodf, Nicola J. Tollidayc, Angela N. Koehlerd, Lisa A. Marcaurellec, Todd R. Golubb, Robert J. Gouldd, Stuart L. Schreiberd,1, and Steven A. Carra,1 aProteomics Platform, bCancer Biology Program, cChemical Biology Platform, dChemical Biology Program, and eStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142; and fChemistry Department, Colorado State University, Fort Collins, CO 80523 Contributed by Stuart L. Schreiber, January 15, 2009 (sent for review December 21, 2008) Most small-molecule probes and drugs alter cell circuitry by interact- known (the ‘‘target I.D. problem’’). It could provide strong clues to ing with 1 or more proteins. A complete understanding of the the mechanisms used by SMs to achieve their recognized actions interacting proteins and their associated protein complexes, whether and it could suggest potential unrecognized actions. the compounds are discovered by cell-based phenotypic or target- Strategies for ‘‘target identification’’ have been developed that based screens, is extremely rare. Such a capability is expected to be rely on genetic (9), computational (10, 11) and biochemical (12) highly illuminating—providing strong clues to the mechanisms used principles. Although several key molecular targets have been iden- by small-molecules to achieve their recognized actions and suggest- tified through affinity chromatography (13–15), it has not been ing potential unrecognized actions. We describe a powerful method widely applied as a general solution to target identification for a combining quantitative proteomics (SILAC) with affinity enrichment number of reasons.
    [Show full text]
  • Visual Gene Network Analysis of Aging-Specific Gene Co-Expression
    4open 2018, 1,4 © B.P. Parida et al., Published by EDP Sciences 2018 https://doi.org/10.1051/fopen/2018004 Available online at: www.4open-sciences.org RESEARCH ARTICLE Visual gene network analysis of aging-specific gene co-expression in human indicates overlaps with immuno-pathological regulations Bibhu Prasad Parida1,*, Biswapriya Biswavas Misra2, Amarendra Narayan Misra3,4 1 Post-Graduate Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Balasore 756020, Odisha, India 2 Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem 27157, NC, USA 3 Central University of Jharkhand, Brambe, Ratu-Lohardaga Road, Ranchi 835205, Jharkhand, India 4 Khallikote University, Berhampur 760001, Odisha, India Received 19 September 2017, Accepted 4 July 2018 Abstract- - Introduction: Aging is a complex biological process that brings about a gradual decline of physiological and metabolic machineries as a result of maturity. Also, aging is irreversible and leads ultimately to death in biological organisms. Methods: We intend to characterize aging at the gene expression level using publicly available human gene expression arrays obtained from gene expression omnibus (GEO) and ArrayExpress. Candidate genes were identified by rigorous screening using filtered data sets, i.e., GSE11882, GSE47881, and GSE32719. Using Aroma and Limma packages, we selected the top 200 genes showing up and down regulation (p < 0.05 and fold change >2.5) out of which 185 were chosen for further comparative analysis. Results: This investigation enabled identification of candidate genes involved in aging that are associated with several signaling cascades demonstrating strong correlation with ATP binding and protease functions.
    [Show full text]
  • Macrophages in Alveolar Aspergillus Fumigatus to Phosphate Oxidase
    Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages This information is current as of September 27, 2021. E. Jean Cornish, Brady J. Hurtgen, Kate McInnerney, Nancy L. Burritt, Ross M. Taylor, James N. Jarvis, Shirley Y. Wang and James B. Burritt J Immunol 2008; 180:6854-6867; ; doi: 10.4049/jimmunol.180.10.6854 Downloaded from http://www.jimmunol.org/content/180/10/6854 References This article cites 80 articles, 29 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/180/10/6854.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 27, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages1 E. Jean Cornish,* Brady J. Hurtgen,* Kate McInnerney,* Nancy L. Burritt,* Ross M.
    [Show full text]
  • The Neuroprotective Role of the GM1 Oligosaccharide, Ii3neu5ac-Gg4, In
    Molecular Neurobiology (2019) 56:6673–6702 https://doi.org/10.1007/s12035-019-1556-8 The Neuroprotective Role of the GM1 Oligosaccharide, 3 II Neu5Ac-Gg4, in Neuroblastoma Cells Elena Chiricozzi1 & Margherita Maggioni1 & Erika di Biase1 & Giulia Lunghi1 & Maria Fazzari1 & Nicoletta Loberto 1 & Maffioli Elisa2 & Francesca Grassi Scalvini2 & Gabriella Tedeschi 2,3 & Sandro Sonnino1 Received: 10 January 2019 /Accepted: 13 March 2019 /Published online: 26 March 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract 3 Recently, we demonstrated that the GM1 oligosaccharide, II Neu5Ac-Gg4 (OligoGM1), administered to cultured murine Neuro2a neuroblastoma cells interacts with the NGF receptor TrkA, leading to the activation of the ERK1/2 downstream pathway and to cell differentiation. To understand how the activation of the TrkA pathway is able to trigger key biochemical signaling, we performed a proteomic analysis on Neuro2a cells treated with 50 μM OligoGM1 for 24 h. Over 3000 proteins were identified. Among these, 324 proteins were exclusively expressed in OligoGM1-treated cells. Interestingly, several proteins expressed only in OligoGM1-treated cells are involved in biochemical mechanisms with a neuroprotective potential, reflecting the GM1 neuroprotective effect. In addition, we found that the exogenous administration of OligoGM1 reduced the cellular oxidative stress in Neuro2a cells and conferred protection against MPTP neurotoxicity. These results confirm and reinforce the idea that the molecular mechanisms underlying the GM1 neurotrophic and neuroprotective effects depend on its oligosaccharide chain, suggesting the activation of a positive signaling starting at plasma membrane level. Keywords GM1 ganglioside . GM1 oligosaccharide chain . TrkA neurotrophin receptor . Plasma membrane signaling . Neuroprotection .
    [Show full text]
  • Inhibition of the FKBP Family of Peptidyl Prolyl Isomerases Induces Abortive Translocation and Degradation of the Cellular Prion Protein
    Inhibition of the FKBP Family of Peptidyl Prolyl Isomerases Induces Abortive Translocation and Degradation of the Cellular Prion Protein by Maxime Sawicki A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Biochemistry University of Toronto © Copyright by Maxime Sawicki 2015 Inhibition of the FKBP Family of Peptidyl Prolyl Isomerases Induces Abortive Translocation and Degradation of the Cellular Prion Protein Maxime Sawicki Master of Science Department of Biochemistry University of Toronto 2015 Abstract Prion disorders are a class of neurodegenerative diseases that feature a structural change of the prion protein from its cellular form (PrPC) into its scrapie form (PrPSc). As these disorders are currently incurable, there is a crucial need for novel therapeutic agents. Here, the FDA-approved immunosuppressive drug FK506 was shown to cause an attenuation in the endoplasmic reticulum (ER) translocation of PrPC by exacerbating an intrinsic inefficiency of PrP’s ER-targeting signal sequence, effectively causing the proteasomal degradation of PrPC. Furthermore, the depletion of FKBP10 also caused the degradation of PrPC but at a later stage following translocation into the ER. Additionally, novel FK506 analogues with reduced immunosuppressive properties were shown to be as efficacious as FK506 in downregulating PrPC. Finally, both FK506 treatment and FKBP10 depletion were shown to reduce the levels of PrPSc in chronically infected cell models. These findings offer a new insight into the development of treatments against prion disorders. ii Acknowledgments The completion of the present thesis would not have been possible without the help and support of a number of people. First and foremost, I would like to thank my supervisor, Dr David Williams, for his constant guidance and expertise that allowed me to successfully complete my degree, as well as my committee members, Dr John Glover and Dr Gerold Schmitt-Ulms, for their invaluable advice and suggestions over the course of this project.
    [Show full text]