Inducible Enzymes in the Inflammatory Response PDF
Preview Inducible Enzymes in the Inflammatory Response
Series Editor Prof. Dr. Michael J. Parnham PLiVA Research Institute Prilaz baruna Filipovica 25 10000 Zagreb Croatia Inducible Enzymes in the Inflammatory Response Derek A. Willoughby Annetle Tomlinson Editors Springer Basel AG Editors Prof. Derek A. Willoughby Dr. Annetle Tomlinson Department of Experimental Pathology St. Bartholomew's and The Royal London School of Medicine and Dentistry Charterhouse Square London, EC1 M 6BQ UK A CIP catalogue record for this book is available from the Library of Congress, Washington D.C., USA Deutsche Bibliothek Cataloging-in-Publication Data Induclble enzymes In the Inflammatory response / ed. by DA Willoughby, A. Tomlinson -Basel ; Boston; Berlin : Birkhăuser, 1999 (progress in inflammation research) ISBN 978-3-0348-9755-6 ISBN 978-3-0348-8747-2 (eBook) DOI 10.1007/978-3-0348-8747-2 The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names, trademarks etc. in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use. This work is subject to copyright. AII rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on micro films or in other ways, and storage in data banks. For any kind of use, permission of the copyright owner must be obtained. © 1999 Springer Basel AG Originally published by Birkhăuser Verlag in 1999 Softcover reprint of the hardcover lSt edition 1999 Printed on acid-free paper produced from chlorine-free pulp. TCF = Cover design: Markus Etlerich, Basel ISBN 978-3-0348-9755-6 987654321 Contents List of contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. vii Preface............................................................................ ix Michel Pairet, Joanne van Rhyn and Manuel Distel Overview of COX-2 in inflammation: from the biology to the clinic............. 1 Adrian J. Hobbs and Salvador Moncada Inducible nitric oxide synthase and inflammation................................ 31 Dean Willis Overview of HO-1 in inflammatory pathologies ................................. 55 Vivienne R. Winrow and David R. Blake Inducible enzymes in the pathogenesis of rheumatoid arthritis. . . . . . . . . . . . . . . . .. 93 Lee D.K. Buttery and Julia M. Polak iNOS and COX-2 in atherosclerosis .............................................. 109 Michael P. Seed, Derek Gilroy, Mark Paul-Clark, Paul R. Colville-Nash, Dean Willis, Annette Tomlinson and Derek A. Willoughby The role of the inducible enzymes cyclooxygenase-2, nitric oxide synthase and heme oxygenase in angiogenesis of inflammation ........................... 125 Sergio H. Ferreira, Fernando Q. Cunha and Stephen Hyslop Role of the inducible forms of cyclooxygenase and nitric oxide synthase in inflammatory pain .................................................... 149 Bernd C. Kieseier and Hans-Peter Hartung Neuroinflammation ............................................................... 169 Contents Annette Tomlinson and Derek A. Willoughby Inducible enzymes in inflammation: advances, interactions and conflicts .. ..187 Index .............................................................................. 207 vi List of contributors David R. Blake, The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL; e-mail: [email protected] Lee D.K. Buttery, Department of Histochemistry, Imperial College School of Medi cine, Hammersmith Campus, Du Cane Road, London W12 ONN, UK; e-mail: [email protected]. uk Paul R. Colville-Nash, Experimental Pathology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Char terhouse Square, London EC1M 6BQ, UK; e-mail: [email protected] Fernando Q. Cunha, Department of Pharmacology, Faculty of Medicine Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto, Sao Paulo 14051-900 Brazil; e-mail: [email protected] Manuel Distel, Department of Medicine, Boehringer Ingelheim International, 300 Beach Road, #14-02/04 The Concourse, Singapore, 199555 Sergio H. Ferreira, Department of Pharmacology, Faculty of Medicine Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto, Sao Paulo 14051-900 Brazil; e-mail: [email protected] Derek Gilroy, Experimental Pathology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charter house Square, London EC1M 6BQ, UK; e-mail: [email protected] Hans-Peter Hartung, Department of Neurology, Karl-Franzens-Universitiit, Auen bruggerplatz 22, A-8036 Graz, Austria; e-mail: [email protected] Adrian J. Hobbs, Wolfson Institute for Biomedical Research, University College London, Rayne Institute, 5 University Street, London WC1E 6JJ, UK List of contributors Stephen Hyslop, Department of Pharmacology, Faculty of Medical Science, Univer sity of Camp in as, Campinas, Sao Paulo, Brazil Bernd Kieseier, Department of Neurology, Karl-Franzens-Universitat, Auenbrugger platz 22, A-8036 Graz, Austria; e-mail: [email protected] Salvador Moncada, Wolfson Institute for Biomedical Research, University College London, Rayne Institute, 5 University Street, London WCIE 6J], UK Michel Pairet, Department of Pulmonary Research, Boehringer Ingelheim, Birk endorfer Str. 65, D-88397 Biberach, Germany; e-mail: [email protected] heim.com Mark Paul-Clark, Experimental Pathology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charter house Square, London ECIM 6BQ, UK; e-mail: [email protected] Julia M. Polak, Department of Histochemistry, Imperial College School of Medi cine, Hammersmith Campus, Du Cane Road, London W12 ONN, UK; e-mail: [email protected]. uk Michael P. Seed, Paneutics, P.O.Box 1358, Swindon SN3 4GP, UK; e-mail: [email protected] Annette Tomlinson, Experimental Pathology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charter house Square, London ECIM 6BQ, UK; e-mail: [email protected] Joanne van Ryn, Department of Pulmonary Research, Boehringer Ingelheim, Birk endorfer Str. 65, D-88397 Biberach, Germany; e-mail: [email protected] Dean Willis, Experimental Pathology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charter house Square, London ECIM 6BQ, UK; e-mail: [email protected] Derek A. Willoughby, Experimental Pathology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Char terhouse Square, London ECIM 6BQ, UK; e-mail: [email protected] Vivienne R. Winrow, Department of Postgraduate Medicine, University of Bath, Claverton Down, Bath BA2 7 AY, UK; e-mail: [email protected] viii Preface This volume will be of great value to all those researchers in the area of the inflam matory response, notably academics, clinicians and members of the pharmaceutical industry. The book has in the main been restricted to three inducible enzymes, namely nitric oxide synthase (iNOS), cyclooxygenase (COX-2) and hemeoxygenase (HO-l), although matrix metalloproteinases, xanthine oxidoreductase and tissue transgluta minases are reviewed. The modulation of these enzymes is viewed as possible novel therapeutic advances in the area of inflammation and also cancer. The latter topic may well be the subject of a further book. It will be interesting to observe the progress of such new therapies in the next decade. Already some of these enzyme modulators have been approved for the treat ment of inflammatory disease, as evidenced by the new families of COX-2 inhibitors. We believe such advances will herald a series of new and exciting agents to be included in the clinician's armamentarium in the constant struggle against inflammatory disease. The editors wish to thank all contributors to this volume on inducible enzymes. It should however be stressed that the views expressed by the authors are personal and do not necessarily reflect those of the editors. Indeed, the reader may find con flicting statements in a number of the chapters. We believe that this is entirely appro priate as this volume reflects the latest work in a rapidly developing area. Finally, the editors would like to express their thanks to Birkhiiuser and their helpful staff, in particular Janine Kern. We hope the reader enjoys the book and finds some thought-provoking issues in this wide spectrum of recent advances in a new and exciting field. Derek Willoughby Annette Tomlinson Overview of COX-2 in inflammation: from the biology to the clinic Michel Pairet, Joanne van Ryn and Manuel Distel* Department of Biological Research and Department of Medicine*, Boehringer Ingelheim, Birkendorfer Str. 65, 0-88397 Biberach/Riss, Germany Discovery of COX-2: Key findings Cyclooxygenase (COX) is part of a bifunctional enzyme, prostaglandin H synthase (PGHS), which catalyzes the first step in the conversion of membrane phospholipids (principally, arachidonic acid) into prostanoids (prostaglandins and thromboxanes). Prostanoids contribute to diverse physiological and pathological processes including inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs), the prototype of which is aspirin, owe their therapeutic effects to blockade of prostaglandin synthe sis through COX blockade [1]. NSAIDs are a heterogenous group of compounds, often chemically unrelated, which nevertheless share therapeutic effects (i.e. anti inflammatory, analgesic and antipyretic) and side effects (i.e. gastrointestinal ero sions, decreased renal function, inhibition of platelet aggregation). Until recently, it had been widely accepted that a common mechanism (COX inhibition) is responsi ble for both the therapeutic and the side-effects of NSAIDs. However, this theory has been refined since the discovery of a second, inducible COX isozyme, COX-2 [2, 3]. It has been proposed that COX-2 inhibition is relevant for the anti-inflam matory effects of NSAIDs, whereas inhibition of constitutive COX-l is responsible for the gastric and renal side effects, as well as for the antithrombotic activity of these agents [4]. The suggestion that an inducible PGHS (for clarity, referred to as COX) existed, arose from studies in the field of inflammation and reproductive biology. As early as 1988, it was noticed that in spite of treatment with antibodies raised against COX purified from ram seminal vesicle (now known to be COX-I), fibroblasts were still able to increase their prostaglandin biosynthetic activity in response to inter leukin-l (IL-l) [5, 6]. Prostaglandin synthase activity was also shown to be strong ly stimulated by bacterial endotoxin in human monocytes in vitro [2] as well as mouse macro phages in vivo [7]. Importantly, this increase was associated with the de novo, glucocorticoid-sensitive synthesis of new COX protein [8]. Studies in the rat ovary also provided evidence that two immunologically distinct forms of COX exist and that one of these two forms can be selectively regulated by hormones Inducible Enzymes in the Inflammatory Response, edited by D.A. Willoughby and A. Tomlinson © 1999 Birkhauser Verlag Basel/Switzerland
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