TNF Pathophysiology

Description

TNF is a multifunctional proinflammatory cytokine central to the development and homeostasis of the immune system and a regulator of cell activation, differentiation and death. Recent decades have seen an enormous scientific and clinical interest in the function of TNF in physiology and disease. A vast amount of data has been accumulated at the biochemical, molecular and cellular level, establishing TNF as a prototype for in-depth understanding of the physiological and pathogenic functions of cytokines. This volume covers several current aspects of TNF regulation and function, including transcriptional and posttranscriptional control mechanisms, cellular modes of action, signaling networks that mediate its effect, involvement in pathogenesis and clinical outcomes of TNF antagonists. It combines basic science at the molecular and cellular level with research in animal models of disease and clinical findings to provide a comprehensive review of recent developments in TNF biology. A thorough understanding of the mechanisms by which this key molecular player is produced and functions to regulate cell biology, immunity and disease postulates novel paradigms on how genes contribute to the development and physiology of biological systems. This book is mandatory reading for molecular and cell biologists, immunologists and clinicians interested in TNF function.

Informations

• Publié par: S. Karger AG
• Date de parution: 18 février 2010
• Nombre de lectures: 0
• EAN13: 9783805593847
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

TNF Pathophysiology. Molecular and Cellular Mechanisms
Current Directions in Autoimmunity
Vol. 11
Series Editor
A.N.Theofilopoulos     La Jolla, Calif.
 
TNF Pathophysiology
Molecular and Cellular Mechanisms
Volume Editors
G. Kollias    Vari
P.P. Sfikakis     Athens
15 figures, 2 in color, and 5 tables, 2010
_________________________
__________________________
George Kollias, PhD Institute of Immunology Biomedical Sciences Research Center ’Alexander Fleming’ Vari, Greece
Petros P. Sfikakis, MD, PhD First Department of Propedeutic and Internal Medicine Laikon Hospital Athens University Medical School Athens, Greece
Library of Congress Cataloging-in-Publication Data
TNF pathophysiology: molecular and cellular mechanisms/volume editors, G. Kollias, P.P. Sfikakis.
p.; cm. - (Current directions in autoimmunity, ISSN 1422-2132; v. 11)
Includes bibliographical references and index.
ISBN 978-3-8055-9383-0 (hard cover: alk. paper)
1. Tumor necrosis factor-Pathophysiology. I. Kollias, G. (George) II. Sfikakis, P.P. (Petros P.)
III. Title: Tumor necrosis factor pathophysiology.
IV. Series: Current directions in autoimmunity, v. 11.1422-2132;
[DNLM:1. Tumor Necrosis Factors-immunology. 2. Tumor Necrosis Factors-physiology. 3. Transcription, Genetic - immunology.
W1 CU788DRv.11 2010 / QW 630 T6267 2010]
QR185.8.T84T543 2010
616.07'9-dc22
2009051929
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and PubMed/MEDLINE.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2010 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel
ISSN 1422-2132
ISBN 978-3-8055-9383-0
e-ISBN 978-3-8055-9384-7
 
Contents
Preface
Kollias, G. (Vari); Sfikakis, P.P. (Athens)
Cellular Mechanisms of TNF Function in Models of Inflammation and Autoimmunity
Apostolaki, M.; Armaka, M.; Victoratos, P.; Kollias, G. (Vari)
Transcriptional Control of the TNF Gene
Falvo, J.V.;Tsytsykova, A.V; Goldfeld, A.E. (Boston, Mass.)
Posttranscriptional Regulation of TNF mRNA: A Paradigm of Signal-Dependent mRNA Utilization and Its Relevance to Pathology
Stamou, P.; Kontoyiannis, D.L. (Vari)
Role of TNF in Pathologies Induced by Nuclear Factor KB Deficiency
Vlantis, K.; Pasparakis, M. (Cologne)
Type I Interferon: A New Player in TNF Signaling
Yarilina, A.; Ivashkiv, L.B. (New York, N.Y.)
T Cells as Sources and Targets of TNF: Implications for Immunity and Autoimmunity
Chatzidakis, I.; Mamalaki, C. (Heraklion)
TNF-α: An Activator of CD4+FoxP3+TNFR2+ Regulatory T Cells
Chen, X.; Oppenheim, JJ. (Frederick, Md.)
TNF and Bone
David, J.-P.; Schett, G. (Erlangen)
TNF-α and Obesity
Tzanavari, T.; Giannogonas, P.; Karalis, K.P. (Athens)
TNF in Host Resistance to Tuberculosis Infection
Quesniaux, V.F.J. (Orleans); Jacobs, M.; Allie, N. (Cape Town); Grivennikov, S. (Orleans/Moscow); Nedospasov, S.A. (Moscow/Berlin); Garcia, I.; Olleros, M.L. (Geneva); Shebzukhov, Y. (Berlin); Kuprash, D. (Moscow); Vasseur, V.; Rose, S.; Court, N.; Vacher, R.; Ryffel, B. (Orleans)
The First Decade of Biologic TNF Antagonists in Clinical Practice: Lessons Learned, Unresolved Issues and Future Directions
Sfikakis, P.P. (Athens)
Author Index
Subject Index
 
Preface
TNF is a pleiotropic cytokine central to the development and homeostasis of the immune system and a regulator of cell activation, differentiation and death. TNF is involved in a multitude of biological processes, such as acute and chronic inflammation, autoimmunity, infection and tumor responses. In the last decades, there has been an enormous scientific and clinical interest in understanding TNF's function in physiology and disease, and a vast amount of data has accumulated at the biochemical, molecular and cellular level, establishing TNF as a prototype for in-depth understanding of a cytokine's physiological and pathogenic functions. Perturbations of TNF and its signals in transgenic models have provided a wealth of information about its function at the organism level as well as created unique animal models for chronic inflammatory disorders. Collectively, this knowledge primed the successful development of anti-TNF therapies for several human diseases and opened new avenues for safer and more effective drug discovery.
The chapters in this volume cover recent developments in TNF regulation and function from a basic molecular and cellular level to whole organism perspectives and their clinical implications. Thorough understanding of the mechanisms by which this key molecular player is produced and functions to regulate cell biology, immunity and disease should set novel paradigms on how genes contribute to biological system development and physiology.
We wish to thank the series editor as well as all the contributing authors for giving us the opportunity to assemble this excellent review volume on TNF biology.
George Kollias, Vari Petros P. Sfikakis, Athens
 
Kollias G, Sfikakis PP (eds): TNF Pathophysiology. Molecular and Cellular Mechanisms. Curr Dir Autoimmun. Basel, Karger, 2010, vol 11, pp 1–26
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Cellular Mechanisms of TNF Function in Models of Inflammation and Autoimmunity
Maria Apostolaki Maria Armaka Panayiotis Victoratos George Kollias
Institute of Immunology, Biomedical Sciences Research Center ‘Alexander Fleming’, Vari, Greece
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Abstract
The TNF/TNF receptor (TNFR) system has a prominent role in the pathogenesis of chronic inflammatory and autoimmune disorders. Extensive research in animal models with deregulated TNF expression has documented that TNF may initiate or sustain inflammatory pathology, while at the same time may exert immunomodulatory or disease-suppressive activities. The TNF/TNFR system encompassing both the soluble and the transmembrane form of TNF with differential biological activities, as well as the differential usage of its receptors, mediating distinct functions, appears to confer complexity but also specificity in the action of TNF. The inherent complexity in TNF-mediated pathophysiology highlights the requirement to address the role of TNF taking into account both proinflammatory tissue-damaging and immunomodulatory functions in a cellular and receptor-specific manner. In this review, we discuss our current understanding of the involvement of TNF in chronic inflammation and autoimmunity, focusing on TNF-mediated cellular pathways leading to the pathogenesis or progression of joint and intestinal inflammatory pathology. Knowledge of the mechanisms by which TNF either initiates or contributes to disease pathology is fundamentally required for the design of safe and effective anti-TNF/TNFR therapies for human inflammatory and autoimmune disorders.
Copyright © 2010 S. Karger AG, Basel
TNF-α is a pleiotropic, proinflammatory mediator whose function is implicated in a wide range of inflammatory, infectious, autoimmune and malignant conditions. TNF is produced in response to infection to confer immunity to the host. While the effect of the TNF in infection is beneficial, tight regulation of TNF production is required to protect the host from the detrimental activities of TNF. Deregulated TNF overex-pression can give rise to chronic inflammatory and autoimmune disorders, such as chronic inflammatory arthritis, inflammatory bowel disease (IBD) and multiple sclerosis (MS). Currently, TNF-blocking agents are widely used and have shown encouraging results for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders including Crohn's disease (CD), ankylosing spondylitis and psoriasis [ 1 - 3 ]. By contrast, anti-TNF therapy in patients with MS led to the adverse outcome worsening disease symptoms [ 4 , 5 ]. Thus, blocking the TNF activity is not always beneficial. Moreover, anti-TNF therapy has led to side effects including opportunistic infections, demyelination, system