DOCSLIB.ORG

Generation Mechanisms of Soluble Cytokine Receptor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Generation Mechanisms of Soluble Cytokine Receptor Mechanisms of Soluble Cytokine Receptor Generation Stewart J. Levine This information is current as J Immunol 2004; 173:5343-5348; ; of September 28, 2021. doi: 10.4049/jimmunol.173.9.5343 http://www.jimmunol.org/content/173/9/5343 Downloaded from References This article cites 113 articles, 70 of which you can access for free at: http://www.jimmunol.org/content/173/9/5343.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • 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 by guest on September 28, 2021 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 © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY BRIEF REVIEWS Mechanisms of Soluble Cytokine Receptor Generation Stewart J. Levine1 Soluble cytokine receptors regulate inflammatory and im- biomarker of T cell activation and tumor burden in IL-2R␣- mune events by functioning as agonists or antagonists of expressing lymphoid neoplasms (3, 4). cytokine signaling. As such, they act within complex recep- Agonistic and antagonistic modulation of cytokine activity by soluble tor systems that include signaling receptors, nonsignaling cytokine receptors decoy receptors, receptor-associated proteins, and soluble The IL-1 and IL-6 receptor systems are paradigms for soluble receptor antagonists. Soluble cytokine receptors can be cytokine receptors that mediate antagonistic and agonistic ef- generated by several mechanisms, which include proteo- fects. Both systems are complex and are regulated by multiple lytic cleavage of receptor ectodomains, alternative splicing cell-associated and soluble receptors, as well as receptor-associ- Downloaded from of mRNA transcripts, transcription of distinct genes that ated proteins. encode soluble cytokine-binding proteins, release of full- Multiple endogenous regulatory mechanisms exist to prevent length receptors within the context of exosome-like vesicles, excessive, proinflammatory IL-1 signaling. The functional and cleavage of GPI-anchored receptors. Furthermore, the IL-1R is a complex comprising the type I IL-1R (IL-1RI), the important role of soluble cytokine receptors in regulating IL-1R accessory protein (IL-1RAcP),2 and IL-1␣ or IL-1␤ (5). host defense mechanisms is evidenced by viruses that en- In contrast, the 60-kDa type II IL-1R (IL-1RII) is a nonsignal- http://www.jimmunol.org/ code soluble homologues of mammalian receptors and ing decoy receptor, because its short 29-aa cytoplasmic domain thereby evade innate host immune responses via the se- lacks a Toll-IL-1R domain (6, 7). IL-1RII can also form a non- questration of essential cytokines. The Journal of Immu- signaling trimeric complex with IL-1 and IL-1RAcP, which se- nology, 2004, 173: 5343–5348. questers essential components of the IL-1RI signaling complex (8, 9). Soluble type II IL-1 receptors (sIL-1RII), which are gen- erated primarily by proteolytic cleavage in response to a variety oluble cytokine receptors, which either attenuate or of stimuli (10), can attenuate excessive IL-1 bioactivity by pref- promote cytokine signaling, are important regulators of erentially binding IL-1␤ (11). Furthermore, the ability of sIL- by guest on September 28, 2021 inflammation and immunity. The key role that soluble S 1RII to bind IL-1␣ and IL-1␤ and inhibit IL-1 signaling is en- cytokine receptors play in preventing excessive inflammatory hanced ϳ100-fold by soluble IL-1RAcP, which is generated by responses is illustrated by the autosomal dominant, autoinflam- alternative splicing rather than by ectodomain cleavage (12). In matory, TNF receptor-associated periodic syndrome (TRAPS), addition, sIL-1RII can bind to and inhibit the processing of which was initially identified in patients with mutations in pro-IL-1␤ precursor to its mature form by the IL-1-converting the extracellular domain of the 55-kDa, type I TNFR enzyme (caspase-1) (13). Thus, multiple regulatory mecha- (TNFRSF1A, TNFR1) that impaired receptor shedding (1). nisms, including the generation of sIL-1RII and sIL-1RAcP, ex- Additional pathophysiologic mechanisms may also exist, as not ist by which excessive IL-1 signaling can be attenuated. all TRAPS-related TNFRSF1A mutations are associated with In contrast to the antagonistic effect of sIL-1RII on IL-1 sig- defective receptor shedding. Patients manifest recurrent epi- naling, soluble IL-6 receptors (sIL-6R␣) are an important sodes of fever, myalgia, rash, abdominal pain, and conjunctivi- mechanism by which IL-6 signaling is amplified. Soluble IL-6 tis that may be attenuated by anti-TNF therapy with a recom- receptors can be generated by two distinct pathways: proteolytic binant soluble human TNFR2-Ig fusion protein (1). Similarly, cleavage that sheds the membrane-bound IL-6R ectodomain or administration of a recombinant soluble human TNFR2-Ig fu- alternative mRNA splicing, with resulting synthesis of an IL- sion protein has been used to modify TNF biological activity 6R␣ that lacks the transmembrane domain (14, 15). Soluble and disease severity in patients with inflammatory arthritides IL-6 receptors bind IL-6 with an affinity similar to the mem- and psoriasis (2). Furthermore, the role of soluble cytokine re- brane IL-6R, thereby prolonging the IL-6 half-life (16). Fur- ceptors in modulating immune events is exemplified by the sol- thermore, binding of the sIL-6R␣/IL-6 complex to the ubiqui- uble IL-2R␣ (IL2R␣, CD25, Tac), which has been used as a tously expressed membrane-bound gp130 confers IL-6 Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, of Health, Building 10, Room 6D03, MSC 1590, Bethesda, MD 20892-1590. E-mail National Institutes of Health, Bethesda, MD 20892 address: [email protected] Received for publication July 20, 2004. Accepted for publication August 20, 2004. 2 Abbreviations used in this paper: IL-1RAcP, IL-1R accessory protein; s, soluble; TACE, TNF-␣-converting enzyme; MMP, matrix metalloprotease; DcR3, decoy receptor 3; L, The costs of publication of this article were defrayed in part by the payment of page charges. ligand; Crm, cytokine response modifying; MT, membrane type. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Address correspondence and reprint requests to Dr. Stewart J. Levine, Pulmonary-Crit- ical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 5344 BRIEF REVIEW: MECHANISMS OF SOLUBLE CYTOKINE RECEPTOR GENERATION signaling capability to cells that do not express IL-6R␣ via a tion of the cysteine thiol group in the cysteine-switch domain process termed “trans-signaling” (17). Trans-signaling via sIL- (42, 43). Second, endogenous signaling via G protein-coupled 6R␣/IL-6 complexes regulates the expression of CXC and CC receptors, such as the protease-activated receptor 1, can induce chemokines and terminates neutrophil recruitment in the set- the TACE-mediated cleavage of the heparin-binding epidermal ting of bacterial infection (18). Furthermore, gp130-linked IL- growth factor with resultant transactivation of the epidermal 6/sIL-6R␣ trans-signaling enhances lymphocyte trafficking growth factor receptor (23, 44, 45). Third, TACE catalytic ac- during febrile inflammatory responses via activation of L-selec- tivity may be regulated via protein-protein interactions with the tin-mediated adhesion (19). Importantly, the trans-signaling TACE intracytoplasmic domain. The mitogen-activated pro- function of the sIL-6R␣-IL-6 complex can be abrogated by the tein kinase ERK, in response to phorbol ester stimulation, phos- soluble form of gp130 (sgp130), which competes with mem- phorylates threonine 735 of the TACE intracytoplasmic tail, brane gp130 for binding of the sIL-6R-IL-6 complex (20). whereas serine 819 undergoes growth hormone-induced phos- phorylation, which may regulate proteolytic activity (46, 47). Generation of soluble cytokine receptors by the proteolytic cleavage of The protein tyrosine phosphatase PTPH1 may negatively reg- ectodomains ulate TACE activity through an interaction between its PDZ Proteolytic cleavage of cell surface receptors is typically cata- domain and the carboxyl terminus of TACE (48). The mitotic lyzed by zinc metalloproteases of the ADAM (a disintegrin and arrest-deficient 2 protein and the scaffolding protein synapse- metalloprotease) family. ADAMs are a large family of type I associated protein 97 have also been identified as potentially transmembrane proteins, with at least 34 named mammalian regulating TACE activity via binding to the TACE intracyto- Downloaded from genes that contain multiple domains, including a prodomain plasmic domain (49, 50). Fourth, TACE undergoes stimula- (that maintains the enzyme in an inactive state via a cysteine- tion-dependent internalization,
Load more

Recommended publications
  • Receptor-Mediated Dimerization of JAK2 FERM Domains Is Required for JAK2 Activation Ryan D Ferrao, Heidi JA Wallweber, Patrick J Lupardus*
    RESEARCH ARTICLE Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation Ryan D Ferrao, Heidi JA Wallweber, Patrick J Lupardus* Department of Structural Biology, Genentech, Inc., South San Francisco, United States Abstract Cytokines and interferons initiate intracellular signaling via receptor dimerization and activation of Janus kinases (JAKs). How JAKs structurally respond to changes in receptor conformation induced by ligand binding is not known. Here, we present two crystal structures of the human JAK2 FERM and SH2 domains bound to Leptin receptor (LEPR) and Erythropoietin receptor (EPOR), which identify a novel dimeric conformation for JAK2. This 2:2 JAK2/receptor dimer, observed in both structures, identifies a previously uncharacterized receptor interaction essential to dimer formation that is mediated by a membrane-proximal peptide motif called the ‘switch’ region. Mutation of the receptor switch region disrupts STAT phosphorylation but does not affect JAK2 binding, indicating that receptor-mediated formation of the JAK2 FERM dimer is required for kinase activation. These data uncover the structural and molecular basis for how a cytokine-bound active receptor dimer brings together two JAK2 molecules to stimulate JAK2 kinase activity. DOI: https://doi.org/10.7554/eLife.38089.001 Introduction Janus kinases (JAKs) are a family of multi-domain non-receptor tyrosine kinases responsible for pleio- tropic regulatory effects on growth, development, immune and hematopoietic signaling (Leonard and O’Shea, 1998). The JAK family consists of four conserved members, including JAK1, *For correspondence: [email protected] JAK2, JAK3, and TYK2, which are differentially activated in response to cytokine and interferon stim- ulation. JAKs are constitutively bound to the intracellular domains of their cognate cytokine signaling Competing interest: See receptors, and are activated after cytokine-mediated dimerization or rearrangement of these recep- page 18 tors establishes a productive receptor signaling complex (Haan et al., 2006).
    [Show full text]
  • Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A.
    [Show full text]
  • Cytokine Nomenclature
    RayBiotech, Inc. The protein array pioneer company Cytokine Nomenclature Cytokine Name Official Full Name Genbank Related Names Symbol 4-1BB TNFRSF Tumor necrosis factor NP_001552 CD137, ILA, 4-1BB ligand receptor 9 receptor superfamily .2. member 9 6Ckine CCL21 6-Cysteine Chemokine NM_002989 Small-inducible cytokine A21, Beta chemokine exodus-2, Secondary lymphoid-tissue chemokine, SLC, SCYA21 ACE ACE Angiotensin-converting NP_000780 CD143, DCP, DCP1 enzyme .1. NP_690043 .1. ACE-2 ACE2 Angiotensin-converting NP_068576 ACE-related carboxypeptidase, enzyme 2 .1 Angiotensin-converting enzyme homolog ACTH ACTH Adrenocorticotropic NP_000930 POMC, Pro-opiomelanocortin, hormone .1. Corticotropin-lipotropin, NPP, NP_001030 Melanotropin gamma, Gamma- 333.1 MSH, Potential peptide, Corticotropin, Melanotropin alpha, Alpha-MSH, Corticotropin-like intermediary peptide, CLIP, Lipotropin beta, Beta-LPH, Lipotropin gamma, Gamma-LPH, Melanotropin beta, Beta-MSH, Beta-endorphin, Met-enkephalin ACTHR ACTHR Adrenocorticotropic NP_000520 Melanocortin receptor 2, MC2-R hormone receptor .1 Activin A INHBA Activin A NM_002192 Activin beta-A chain, Erythroid differentiation protein, EDF, INHBA Activin B INHBB Activin B NM_002193 Inhibin beta B chain, Activin beta-B chain Activin C INHBC Activin C NM005538 Inhibin, beta C Activin RIA ACVR1 Activin receptor type-1 NM_001105 Activin receptor type I, ACTR-I, Serine/threonine-protein kinase receptor R1, SKR1, Activin receptor-like kinase 2, ALK-2, TGF-B superfamily receptor type I, TSR-I, ACVRLK2 Activin RIB ACVR1B
    [Show full text]
  • Mechanism of Homodimeric Cytokine Receptor Activation and Dysregulation by Oncogenic Mutations
    This is a repository copy of Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/155270/ Version: Accepted Version Article: Wilmes, Stephan, Hafer, Maximillian, Vuorio, Joni et al. (15 more authors) (2020) Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. Science. pp. 643-652. ISSN 0036-8075 https://doi.org/10.1126/science.aaw3242 Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Submitted Manuscript: Confidential Title: Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations Authors: 5 Stephan Wilmes1, 2*, Maximillian Hafer1*, Joni Vuorio3,4, Julie A. Tucker5, Hauke Winkelmann1, Sara Löchte1, Tess A. Stanly5, Katiuska D. Pulgar Prieto5, Chetan Poojari3, Vivek Sharma3,6, Christian P. Richter1, Rainer Kurre1, Stevan R. Hubbard7, K. Christopher Garcia8,9, Ignacio Moraga2, Ilpo Vattulainen3,4,10†, Ian S. Hitchcock5† and Jacob Piehler1† Affiliations: 10 1 Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
    [Show full text]
  • TNF Decoy Receptors Encoded by Poxviruses
    pathogens Review TNF Decoy Receptors Encoded by Poxviruses Francisco Javier Alvarez-de Miranda † , Isabel Alonso-Sánchez † , Antonio Alcamí and Bruno Hernaez * Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Campus de Cantoblanco, Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain; [email protected] (F.J.A.-d.M.); [email protected] (I.A.-S.); [email protected] (A.A.) * Correspondence: [email protected]; Tel.: +34-911-196-4590 † These authors contributed equally. Abstract: Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF- based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules. Keywords: poxvirus; immune evasion; tumour necrosis factor; tumour necrosis factor receptors; lymphotoxin; inflammation; cytokines; secreted decoy receptors; vaccinia virus; ectromelia virus; cowpox virus Citation: Alvarez-de Miranda, F.J.; Alonso-Sánchez, I.; Alcamí, A.; 1. TNF Biology Hernaez, B. TNF Decoy Receptors TNF is a potent pro-inflammatory cytokine with a broad range of biological effects, Encoded by Poxviruses. Pathogens ranging from the activation of inflammatory gene programs to cell differentiation or 2021, 10, 1065.
    [Show full text]
  • Stony Brook University
    SSStttooonnnyyy BBBrrrooooookkk UUUnnniiivvveeerrrsssiiitttyyy The official electronic file of this thesis or dissertation is maintained by the University Libraries on behalf of The Graduate School at Stony Brook University. ©©© AAAllllll RRRiiiggghhhtttsss RRReeessseeerrrvvveeeddd bbbyyy AAAuuuttthhhooorrr... Regulation of Dimerization and Activation of the Thrombopoietin Receptor A Dissertation Presented by Miki Itaya to The Graduate School in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biochemistry and Structural Biology Stony Brook University December 2012 Copyright by Miki Itaya 2012 Stony Brook University The Graduate School Miki Itaya We, the dissertation committee for the above candidate for the Doctor of Philosophy degree, hereby recommend acceptance of this dissertation. Steven O. Smith, Ph.D. - Dissertation Advisor Professor, Department of Biochemistry and Cell Biology Erwin London, Ph.D. - Chairperson of Defense Professor, Department of Biochemistry and Cell Biology Robert C. Rizzo, Ph.D. Associate Professor, Department of Applied Mathematics and Statistics Nancy Reich Marshall, Ph.D. Professor, Department of Molecular Genetics and Microbiology This dissertation is accepted by the Graduate School Charles Taber Interim Dean of the Graduate School ii Abstract of the Dissertation Regulation of Dimerization and Activation of the Thrombopoietin Receptor by Miki Itaya Doctor of Philosophy in Biochemistry and Structural Biology Stony Brook University 2012 The thrombopoietin receptor (TpoR) is
    [Show full text]
  • The Function of CD27 Costimulation in the Activation and Fate Decisions of CD8+ T Cells
    The function of CD27 costimulation in the activation and fate decisions of CD8+ T cells Han Dong Zhengzhou, Henan Province, China B.Sc, Zhejing University, 2009 A Dissertation presented to the Graduate Faculty of the University of Virginia in Candidacy for the Degree of Doctor of Philosophy Department of Experimental Pathology University of Virginia May 2015 ! i! Abstract CD8+ cytotoxic T lymphocytes are critical components of adaptive immunity against a variety of intracellular pathogens, and can play a key role in the control of tumors. Effective vaccination strategies against viral infections and tumors will likely require the development of potent CD8+ T cell responses, which are constituted by the expansion of robust primary CD8+ T cell populations and the establishment of long-lasting memory. Fully functional CD8+ T cell responses are highly dependent upon CD4+ helper T cells and Signal 3 inflammatory cytokine pathways. CD4+ T cells have been demonstrated to play a critical role in inducing the expression of CD70, the ligand for CD27, on dendritic cells. However, it is not clear to what extent the ‘help’ provided by CD4+ T cells is manifest via CD70, or how CD70-mediated stimulation of CD8+ T cells is integrated with signals that emanate from Signal 3 pathways, such as type-1 interferon (IFN-1) and IL- 12. In this work, by enforcing or abrogating CD27 function by genetic or protein intervention in murine models, we sought to identify the function of CD27 costimulation in the activation and fate decisions of CD8+ T cells, to determine the extent it resembles CD4+ T cell help, and how inflammation impacts the relative importance of CD70-CD27 interactions in CD8+ T cell primary responses and CD8+ T cell memory.
    [Show full text]
  • Immuno-Endocrine Interactions in Intestinal Inflammation
    IMMUNO-ENDOCRINE INTERACTIONS IN INTESTINAL INFLAMMATION PhD Thesis- Shajib, MS; McMaster University-Medical Sciences Immuno-endocrine interactions in intestinal inflammation By Md. Sharif Shajib, BSc. (Hons) A Thesis Submitted to the School of Graduate Studies in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy McMaster University © Copyright by Md. Sharif Shajib, 2017. PhD Thesis- Shajib, MS; McMaster University-Medical Sciences Descriptive notes Doctor of Philosophy (2017) McMaster University, Hamilton, Ontario (Medical Sciences) TITLE Immuno-endocrine interactions in intestinal inflammation AUTHOR Md. Sharif Shajib, BSc. (Hons) SUPERVISOR Dr. Waliul I. Khan NUMBER OF PAGES: XX, 292. II PhD Thesis- Shajib, MS; McMaster University-Medical Sciences Lay abstract The gut produces most of the serotonin found in our body, where it regulates many normal functions. A group of special cells, named enterochromaffin cells, produces nearly all of the serotonin in the gut. In diseases of the gut, especially ones that involve inflammation resulting in symptoms like abdominal pain, diarrhea and bleeding, the number of these cells and serotonin concentration are different from that in the normal gut. I found that these changes are controlled by a particular protein produced by immune cells, called interleukin-13, and alteration in serotonin levels, in turn, contributes to the inflammatory process. Our laboratory experiments with cells and animals establish this connection between interleukin-13 and serotonin in gut inflammation. We further confirm this association between interleukin-13 and serotonin in human inflammatory bowel disease. Moreover, we identify a potential genetic cause of these changes in serotonin concentrations which may ultimately result in inflammatory bowel disease.
    [Show full text]
  • Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes
    Tohoku J. Exp. Med., 2011,Differential 223, 161-176 Gene Expression in OPCs, Oligodendrocytes and Type II Astrocytes 161 Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes Jian-Guo Hu,1,2,* Yan-Xia Wang,3,* Jian-Sheng Zhou,2 Chang-Jie Chen,4 Feng-Chao Wang,1 Xing-Wu Li1 and He-Zuo Lü1,2 1Department of Clinical Laboratory Science, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China 2Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, P.R. China 3Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China 4Department of Laboratory Medicine, Bengbu Medical College, Bengbu, P.R. China Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs.
    [Show full text]
  • CD95 Ligand - Death Factor and Costimulatory Molecule?
    Cell Death and Differentiation (2003) 10, 1215–1225 & 2003 Nature Publishing Group All rights reserved 1350-9047/03 $25.00 www.nature.com/cdd Review CD95 ligand - death factor and costimulatory molecule? O Janssen*,1, J Qian1, A Linkermann1 and D Kabelitz1 Tissue and Cellular Expression of CD95L 1 Institute for Immunology, Medical Center Schleswig-Holstein, Campus Kiel, Michaelisstrasse 5, D-24105 Kiel, Germany The CD95 ligand (CD95L, Apo-1L, FasL, CD178) is a 281- * Corresponding author: O Janssen. Tel: þ 49-431-5973377; Fax: þ 49-431- amino-acid-containing type II transmembrane protein of the 5973335; E-mail: [email protected] TNF family of death factors (Figure 1).1 Its death-inducing function is best documented in the context of activation- Received 24.4.03; revised 12.6.03; accepted 20.6.03; published online 1 August 2003 induced cell death (AICD) in T cells.2 CD95L is expressed as a Edited by T Ferguson death factor in cytotoxic T lymphocytes (CTL) to kill virally infected or transformed target cells and in natural killer (NK) cells, where it is upregulated by CD16 engagement and 3 Abstract cytokines including IL-2 and IL-12. Similarly, high levels of intracellular CD95L have been detected in monocytic cells The CD95 ligand is involved as a death factor in the with an inducible release upon activation.4 Under physiologi- regulation of activation-induced cell death, establishment cal conditions, CD95L is implicated in the control of erythroid of immune privilege and tumor cell survival. In addition, differentiation,5 angiogenesis in the eye6 and skin home- 7 CD95L may serve as a costimulatory molecule for T-cell ostasis.
    [Show full text]
  • Due to Interleukin-6 Type Cytokine Redundancy Only Glycoprotein 130 Receptor Blockade Efficiently Inhibits Myeloma Growth
    Plasma Cell Disorders SUPPLEMENTARY APPENDIX Due to interleukin-6 type cytokine redundancy only glycoprotein 130 receptor blockade efficiently inhibits myeloma growth Renate Burger, 1 Andreas Günther, 1 Katja Klausz, 1 Matthias Staudinger, 1 Matthias Peipp, 1 Eva Maria Murga Penas, 2 Stefan Rose-John, 3 John Wijdenes 4 and Martin Gramatzki 1 1Division of Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany; 2Institute of Human Genetics, Christian-Albrechts-University Kiel and Uni - versity Medical Center Schleswig-Holstein, Kiel, Germany; 3Department of Biochemistry, Christian-Albrechts-University of Kiel, Medical Faculty, Germany and 4Gen-Probe/Diaclone SAS, Besançon, France ©2017 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2016.145060 Received: February 25, 2016. Accepted: September 14, 2016. Pre-published: September 22, 2016. Correspondence: [email protected] SUPPLEMENTARY METHODS Cell lines and culture Cell lines INA-6, INA-6.Tu1 and B9 were cultivated in RPMI-1640 with GlutaMax™-I, 25 mM HEPES (Gibco®/Life Technologies GmbH, Darmstadt, Germany), 10% (v/v) heat-inactivated fetal bovine serum (FBS) (HyClone; Perbio Science, Erembodegen, Belgium), and antibiotics (R10+ medium) supplemented with 2.5 ng/ml recombinant huIL-6 (Gibco®/Life Technologies GmbH, Darmstadt, Germany). The cell lines are routinely confirmed to be negative for mycoplasma contamination (Venor™GeM Mycoplasma Detection Kit, Sigma-Aldrich, St. Louis, MO). Cytokines and other reagents Recombinant huIL-6 was purchased from Gibco®/Life Technologies (Darmstadt, Germany), huLIF was from Reliatech (Wolfenbüttel, Germany). Recombinant muIL-6 was obtained from Peprotech (Rocky Hill, NJ), and soluble muIL-6R was from R&D Systems (Minneapolis, MN).
    [Show full text]
  • Decoy Strategies: the Structure of TL1A:Dcr3 Complex
    Structure Article Decoy Strategies: The Structure of TL1A:DcR3 Complex Chenyang Zhan,1 Yury Patskovsky,1 Qingrong Yan,2 Zhenhong Li,1 Udupi Ramagopal,1 Huiyong Cheng,1 Michael Brenowitz,1 Xiao Hui,3 Stanley G. Nathenson,2,4 and Steven C. Almo1,5,* 1Department of Biochemistry 2Department of Cell Biology 3Department of Developmental and Molecular Biology 4Department of Microbiology and Immunology 5Department of Physiology and Biophysics Albert Einstein College of Medicine, Bronx, NY 10461, USA *Correspondence: [email protected] DOI 10.1016/j.str.2010.12.004 SUMMARY domains (CRDs), which bind the interprotomer grooves formed between adjacent ligand monomers. This mode of interaction Decoy Receptor 3 (DcR3), a secreted member of the results in ligand:receptor assemblies with 3:3 stoichiometries Tumor Necrosis Factor (TNF) receptor superfamily, that span two interacting cells. The ligand-mediated clustering neutralizes three different TNF ligands: FasL, LIGHT, of TNFRs directs the recruitment of signaling adaptor proteins, and TL1A. Each of these ligands engages unique such as TNF receptor associated factors (TRAFs) or death signaling receptors which direct distinct and critical domain adaptor proteins, and initiates diverse downstream immune responses. We report the crystal structures signaling pathways. Some TNFRs are also produced as soluble forms due to alter- of the unliganded DcR3 ectodomain and its complex nate mRNA splicing or selective proteolytic cleavage (Cheng with TL1A, as well as complementary mutagenesis et al., 1994; Locksley et al., 2001; Van Zee et al., 1992). The met- and biochemical studies. These analyses demon- alloprotease-mediated cleavage of two TNF-a receptors (TNFR1 strate that DcR3 interacts with invariant backbone and TNFR2) has been reported to attenuate proinflammatory and side-chain atoms in the membrane-proximal TNF-a-associated signaling, possibly by reducing the amount half of TL1A which supports recognition of its three of cell surface receptors and by the sequestration/neutralization distinct TNF ligands.
    [Show full text]