ACUTE PHASE PROTEINS – REGULATION AND FUNCTIONS OF ACUTE PHASE PROTEINS Edited by Francisco Veas Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins Edited by Francisco Veas Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Davor Vidic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright Ali Mazraie Shadi, 2011. Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins, Edited by Francisco Veas p. cm. ISBN 978-953-307-252-4 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Transcriptional Regulation of Acute Phase Protein Genes 1 Claude Asselin and Mylène Blais Chapter 2 Acute Phase Proteins: Structure and Function Relationship 25 Sabina Janciauskiene, Tobias Welte and Ravi Mahadeva Chapter 3 Regulatory Mechanisms Controlling Inflammation and Synthesis of Acute Phase Proteins 61 Jolanta Jura and Aleksander Koj Chapter 4 IL-22 Induces an Acute-Phase Response Associated to a Cohort of Acute Phase Proteins and Antimicrobial Peptides as Players of Homeostasis 85 Francisco Veas and Gregor Dubois Chapter 5 Hemostatic Soluble Plasma Proteins During Acute-Phase Response and Chronic Inflammation 105 Irina I. Patalakh Chapter 6 Brain Barriers and the Acute-Phase Response 137 Fernanda Marques, Margarida Correia-Neves, João Carlos Sousa, Nuno Sousa and Joana Almeida Palha Chapter 7 Acute Phase Proteins: Ferritin and Ferritin Isoforms 153 Alida Maria Koorts and Margaretha Viljoen Chapter 8 The Hepatic Acute Phase Response to Thermal Injury 185 Marc G. Jeschke Chapter 9 Adipocytokines in Severe Sepsis and Septic Shock 211 Hanna Dückers, Frank Tacke, Christian Trautwein and Alexander Koch VI Contents Chapter 10 Haptoglobin Function and Regulation in Autoimmune Diseases 229 Georgina Galicia and Jan L. Ceuppens Chapter 11 Acute-Phase Proteins: Alpha -1- Acid Glycoprotein 247 C. Tesseromatis, A. Alevizou, E. Tigka and A. Kotsiou Chapter 12 Haptoglobin and Hemopexin in Heme Detoxification and Iron Recycling 261 Deborah Chiabrando, Francesca Vinchi, Veronica Fiorito and Emanuela Tolosano Chapter 13 Haptoglobin is an Exercise-Responsive Acute-Phase Protein 289 Cheng-Yu Chen, Wan-Ling Hsieh, Po-Ju Lin, Yung-Liang Chen and Simon J. T. Mao Chapter 14 Acute Phase Proteins in Prototype Rheumatic Inflammatory Diseases 303 Katja Lakota, Mojca Frank, Olivio Buzan, Matija Tomsic, Blaz Rozman and Snezna Sodin-Semrl Chapter 15 Role of Fetuin-A in Injury and Infection 329 Haichao Wang, Wei Li, Shu Zhu, Ping Wang and Andrew E. Sama Chapter 16 Neutrophil Gelatinase Associated Lipocalin: Structure, Function and Role in Human Pathogenesis 345 Subhankar Chakraborty, Sukhwinder Kaur, Zhimin Tong, Surinder K. Batra and Sushovan Guha Preface A dynamic physiological equilibrium known under the name of homeostasis is determined by endogenous factors and by interactions of organisms with their exogenous environment. To preserve this equilibrium state, which reflects a healthy state of the individual, the organism is constantly sensing and adjusting levels of factors involved in these mechanisms participating to the equilibrium. Most of these homeostatic factors are well preserved because of their highly relevant functional importance for life. Depending on species, some of them could vary in their expression, and will be adapted to the encountered situations. These conserved innate strategies will not only have effects on individuals, but also on populations and moreover in their relations with the environmental stimuli (temperature, humidity, chemical, infections, diet). A broad and conserved response to internal or external stimuli will very quickly be induced, in a matter of minutes, to generate a cascade of inflammatory processes in order to reestablish the homeostatic state in the organism as soon as possible. Stimuli inducing homeostatic changes can be of different nature: trauma, toxin, infection, genetic dysfunction, childbirth, etc. The process of acute inflammation is initiated by cells already present in all tissues, including macrophages, dendritic cells, Kupffer cells. These cells harbor surfaces pattern recognition receptors (PRRs), which recognize at the beginning of the infectious process, exogenous molecules broadly shared by pathogens (pathogen- associated molecular patterns, PAMPs), but not by the host. Important addition to PAMPs, but to a lesser extent, are non-pathogenic microorganisms which also harbor the highly conserved molecules recognized as non-self that will induce a very low level of local inflammation. This response is amplified by endogenously released mediators and by co-factors or concomitant stressful events (burn, trauma, apoptosis, etc.) as well as molecular mechanisms involved in the vicious circle of destruction- reconstruction of vessels and tissues, acting through injury-associated signals known as Damage-Associated Molecular Patterns (DAMPs or Alarmins) and acute phase proteins. Moreover, some of the APP are also antimicrobials exhibiting a wide range of defensive functions, that alongside their repair functions help to reduce pathologic damage, and consequently help to restore the homeostasis. X Preface The maintaining of homeostasis requires rapid and short acute inflammatory responsiveness. Inflammatory mediators, including APP, exhibit short half-lives, which ensures that the inflammatory phenomenon ceases as soon as the stimulus disappears. In contrast, the presence of APP at increased levels can be considered as sensitive sensor of homeostasis disruption. Persisting levels of APP are observed in chronic diseases. The inflammation process is strongly associated with vascular changes as vasodilation and its resulting increased blood flow causes the redness (rubor) and increased heat (calor) as well as an augmented permeability resulting in a plasma protein leakage into the tissue causing edema, observed as swelling (tumor) and pain (dolor). Activated cells will then migrate the injury site. Depending on the intensity of inflammation and the organ in question, it is possible to observe the fifth component of inflammation as described by Aulus Cornelius Celsus in his treatise On Medicine (1st century BC) - loss of function (functio laesa) that results from cross talk between inflammation process and the central nervous system. The two volumes of Acute Phase Proteins book consist of chapters that give a large panel of fundamental and applied knowledge on one of the major elements of the inflammatory process during the acute phase response, i.e., the acute phase proteins expression and functions that regulate homeostasis. We have organized this book in two volumes - the first volume, mainly containing chapters on structure, biology and functions of APP, the second volume discussing different uses of APP as diagnostic tools in human and veterinary medicine. By using an open access publishing model, we wanted to facilitate a large access to readers from different places all over the world, notably developing countries, with the aim of contributing to a better world of knowledge. We also wanted to dedicate this book to our colleagues from both academia and industry in order to create values of knowledge in the field of control of inflammatory processes occurring in diverse diseases to improve the management efficacy of a more personalized medicine. At present, CRP and SAA are the most responsive APP during inflammatory processes in humans. In most cases they are associated with the erythrocyte sedimentation rate (ESR) marker, which strongly depends on high fibrinogen concentration allowing the sticking between erythrocytes. In mice, some changes are also reported for SAA. Despite the fact that the field of inflammation and its associated factors, including APP, cytokines antimicrobial peptides, etc., have been observed and studied from very ancient times, a detailed and updated knowledge is urgently needed as well as pivotal in future research for an integrative personalized medicine that takes into account several parameters including nutritional and systemic factors. Particularly, with the help of large-scale identification methods, such as proteomics, transcriptomics, metabolomics and interactomics, it should be important to get more precise data on kinetic and on the individual role of each APP within the network of the acute phase responsive elements. Thus, it should be important, in this research, to [...]... Effects of hepatocye nuclear factor-4alpha on the regulation of the hepatic acute phase response J Mol Biol., 371(2): 323-335 Wang, Z., & Burke, P A (2008) Modulation of hepatocyte nuclear factor-4alpha function by the peroxisome-proliferator-activated receptor-gamma co-activator-1alpha in the acute- phase response Biochem J., 415(2): 289-296 24 Acute Phase Proteins – Regulation and Functions of Acute Phase. .. cholesterol and lipoprotein metabolism as well as glucose 14 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins and fatty acid metabolism (Shih et al., 2001; Armendariz and Krauss, 2009) In addition, HNF-1α activates numerous APP genes, including SERPINA1, ALB, TRR, CRP, FBG, LBP and VTN Indeed, expression of these APP genes is reduced in HNF-1α knockout mice (Armendariz and Krauss,... HNF-1α and HNF4α, mediate part of the inflammatory response through the establishment of enhancerspecific chromatin domains, like PU.1 in macrophages? 12 Acknowledgement This work is supported by the Crohn’s and Colitis Foundation of Canada Claude Asselin is a member of the FRSQ-funded Centre de recherche clinique Étienne-Lebel 18 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins. .. absence of C/EBPβ, this element is bound by a negative regulator of C/EBP activities, namely C/EBPζ (Oyadomari and Mori, 2004), and by RBP-Jκ, a transcriptional repressor of Notch signaling (Sanalkumar et al., 2010), which insures C/EBPζ binding to the C/EBP site (Singh et al., 2007) Cytokine 10 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins stimulation leads to a replacement of. .. modulates C/EBP-dependent transcriptional activation of APP genes (Rousseau et al., 2008) Indeed, GATA4 represses 16 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins C/EBP isoform activation of the KNG1 and HP promoters GATA4 interacts with the C/EBPδ C-terminal DNA-binding domain GATA4 overexpression leads to decreases in C/EBPβ and C/EBPδ basal as well as IL-1β-induced protein... 2004) Recent analysis of Nos2 activation by LPS in macrophages suggests that c-Jun phosphorylation is central to insure 8 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins NCoR promoter discharge (Huang et al., 2009) Indeed, LPS treatment leads to recruitment of NF-κB p65 to a NF-κB DNA-binding site near the AP-1 element NF-κB p65 recruits the inhibitor of κB kinase IKKε (Nomura... chemokines and antibacterial peptides, among others These genes are temporally regulated, with early expressed or primary response genes, and late expressed or secondary response genes In contrast to primary 2 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins response genes, secondary response genes need new protein synthesis to establish full expression patterns This complex regulation. .. – intrinsic signals, resulting in stress and metabolic activation or repression of specific inflammatory response gene expression programs 7 The acute phase- response and acute phase proteins Tissue injury, trauma or infection lead to complex and systemic reactions referred to as the acute- phase reaction (APR) (Epstein, 1999) The APR is part of a repertoire of cell responses to inflammation, characterized... Enhancer-specific signature elements, namely high levels of the H3K4 monomethylated mark as opposed to the trimethylated mark (Heintzman et al., 2007), and bound acetyltransferase coregulator p300, have allowed genome-wide enhancer identification (Heintzman et al., 2009; Visel et 6 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins primary response gene protein synthesis not required... (2009) Control of inducible gene expression by signal-dependent transcriptional elongation Cell, 138(1): 129-145 20 Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins Heintzman, N D., Stuart, R K., Hon, G., Fu, Y., Ching, C W., Hawkins, R D., Barrera, L O., Van Calcar, S., Qu, C., Ching, K A., Wang, W., Weng, Z., Green, R D., Crawford, G.E., & Ren, B (2007) Distinct and predictive . ACUTE PHASE PROTEINS – REGULATION AND FUNCTIONS OF ACUTE PHASE PROTEINS Edited by Francisco Veas Acute Phase Proteins – Regulation and Functions of Acute Phase. Inflammation and Synthesis of Acute Phase Proteins 61 Jolanta Jura and Aleksander Koj Chapter 4 IL-22 Induces an Acute- Phase Response Associated to a Cohort of Acute Phase Proteins and Antimicrobial. edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Acute Phase Proteins – Regulation and Functions of Acute Phase Proteins,