Regulation Of Chemokine Receptor Interactions And Functions
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Regulation of Chemokine- Receptor Interactions and Functions by Martin J. Stone (Ed.) Pdf
A hallmark of inflammation is the accumulation of leukocytes, which can serve to remove pathogens and necrotic tissue, but may also damage healthy tissue and exacerbate the inflammatory response. Our understanding of leukocyte recruitment in inflammation was revolutionized in the late 1980s by the discovery of chemokines (chemotactic cytokines), a family of small, secreted proteins that induce migration of selective subsets of leukocytes. Shortly afterwards, chemokines were found to exert their functions through the now familiar chemokine receptors, members of the G protein-coupled receptor superfamily. As their physiological and pathological functions were elucidated, chemokine receptors have become popular targets for drug development in inflammatory diseases as well as cancer metastasis and HIV infection. Extensive research has revealed that the functions of chemokines and their receptors are regulated at numerous levels, including: genetic mutations/polymorphisms; control of expression levels; ligand internalization via functional or decoy receptors; intrinsic selectivity of chemokine-receptor binding; hetero- or homo-oligomerization of chemokines or of receptors; alternative signalling pathways; interaction of chemokines with glycosaminoglycans; post-translational modifications; and binding to pathogen-derived inhibitors. This Special Issue of IJMS focused on the natural and pharmacological mechanisms by which the activities of chemokines and their receptors can be regulated.
Chemokines by Astrid E. Cardona,Eroboghene E. Ubogu Pdf
Chemokines constitute a large family of structurally similar cytokines that contain a signature of conserved cysteine residues joined by disulfide bridges. Binding of chemokines to specific G protein-coupled receptors followed by downstream signaling defines their biological function. Initially, chemoattraction was the key function linked to chemokines/chemokine receptors; however, in recent years, it has become clear that chemokine ligand-receptor interactions can also modulate cellular activation, survival, and proliferation, among other functions in homeostatic and diseased states. Importantly, major advances in our understanding of chemokine biology have led to chemokine receptors becoming specific therapeutic targets with great potential. In Chemokines: Methods and Protocols, expert researchers provide practical information regarding experimental models and state of the art protocols used to delineate chemokine/chemokine receptor function and their applications in health and disease. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and easy to use, Chemokines: Methods and Protocols aims to reveal key protocols of functional and descriptive chemokine ligand/receptor assays that will be of practical significance to graduate students, post-doctoral fellows, trainees, and researchers in academia and industry.
Pathogen-Derived Immunomodulatory Molecules by Padraic G. Fallon Pdf
Pathogen-Derived Immunomodulatory Molecules is a book title that may require some explanation. Pathogens that are present today have evolved following a long association with man and have developed unique strategies that have been optimized by natural selection to subvert the host immunity. As we approach the 200th anniversary of Charles Darwin’s birth, it is appropriate to appreciate that Darwin recognized that pathogens (infections) play a significant and potent role in natural selection, encompassed by the concept “infection begets natural selection”. This book therefore examines the molecules that pathogens produce, which can modulate or usurp the functions of the immune system. The idea of using molecules from pathogens as a therapeutic is an ancient concept in medicine. Such a strategy is exemplified by vaccination, with pathogen molecules employed to induce protective immunity against the given or related species of pathogen. The following chapters explore the concept of using pathogen-derived immune modulating molecules as a therapy. In doing so, they may provide the drug cabinet of the future for treating a spectrum of unrelated disease. Herein, a range of immune modulating molecules or strategies from various pathogens is examined in one volume. The intention of the book was to have chapters addressing immunomodulating molecules from different pathogens. The range of pathogens considered includes bacteria (chapters by Williams, van Strijp and Rooijakkers), viruses (chapters by Bowie, McFadden), protozoan parasites (Aliberti), helminths (Harnett, Fallon), fungi (Sorrell) and parasitic ticks (Anguita). Chapters also address specific immunomodulatory molecules or strategies. The diversity of aspects addressed in the book is highlighted by Lucas and colleagues review of the ‘saga’ of viral serine proteinase inhibitors, with a focus on Serp-1, the first new generation of pathogen immunomodulatory molecule currently in clinical trials. While Elliott and Weinstock have contributed a provocative chapter exploring the use of live parasitic helminth infections as a therapeutic strategy for immune-mediated diseases; indeed trials have already been completed for such an approach. With respect to pathogens usurping an immune pathway, Alcami and colleagues here reviewed the growing number of pathogens that have evolved a range of molecules that can modify many aspects of the chemokine system. This book is timely due to the need to expand the horizons of conventional drug discovery. A trend in the biopharmaceutical pipeline of fewer drugs to market is illustrated by USA FDA in 2007 approving the lowest number of new molecular entities since 1983. As the drug discovery and development industry broadens its search for new drugs to less traditional strategies, this book will be a reference to the potential for exploiting pathogen as a source of the anti-inflammatory drugs of the future. Finally, this book whets the appetite for the reader, whether in academia or industry, to explore opportunities for exploiting pathogens for the discovery of new processes in immunobiology and, ultimately, for development of new therapies for human inflammatory diseases.
Chemokines and Viral Infection by Thomas E. Lane Pdf
Chemokines represent a family of over 40 small proteins that, for the most part, are secreted into the environment and function by binding to G protein-coupled receptors (GPCRs) that are expressed on numerous different cell types. When initially identified close to 30 years ago, these molecules were associated with various human inflammatory diseases and it was recognized that expression may be integral in leukocyte recruitment to inflamed tissue. Within a relatively short period of time, early participants within the field determined that these proteins displayed distinct and conserved structural features and exerted potent chemotactic effects on defined lymphocyte subsets. There are now four sub-families of chemokines identified based on defined structural criteria relating to the positional location of conserved cysteine residues within the amino-terminus of the protein. Chemokines are now recognized as important in numerous biological processes ranging from maintaining the organizational integrity of secondary lymphoid tissue to participating in various aspects of both innate and adaptive immune responses following microbial infection.
Chemokine Receptors in Cancer by Amy M. Fulton Pdf
Chemokines are a superfamily of low molecular weight cytokines that were initially described based on their ability to induce the directed migration of leukocytes to sites of inflammation or injury. In humans, there are approximately 45 chemokines that bind to 19 G-protein-coupled receptors. In addition to mediating cellular migration, chemokines have now been shown to affect many cellular functions including survival, adhesion, invasion, proliferation, and to regulate circulating chemokine levels. Although chemokine receptors were first described on leukocytes, it is now appreciated that chemokine receptors are also expressed by many other cells including endothelial and epithelial cells. Since the first description of chemokine receptors on malignant cells in 2001, an extensive literature has developed describing the expression and function of chemokine receptors in many malignancies. These studies support the initial hypothesis that malignant cells use chemokine receptors to migrate to distant sites of ligand expression and that expression of certain receptors is associated with a poor prognosis. It has also become apparent that malignancies of different tissues may use a diverse profile of chemokine receptors and that the same receptor may mediate metastasis to different sites in tumors of different histological origins. Receptor function may also maintain survival and expansion of the primary tumor.
Sensory Nerves by Brendan J. Canning,Domenico Spina Pdf
The intention of this book is to provide a comprehensive and contemporary review of the biology of sensory nerves. The book is unique, as it comprehensively covers the role of sensory nerves across many therapeutic areas.
The Orthopoxviruses presents knowledge and comprehensive and integrated picture of orthopoxviruses. The book looks into the molecular biology of this genusof viruses, particularly, the structure and chemical composition of the virion, replication, morphogenesis, pathogenesis, pathology, and immunology of this virus’ infections. It also elucidates the global spread, control, and eradication of smallpox. Additionally, the book describes a potentially important use of vaccinia virus, namely, its use as a vector for genes from other viruses, bacteria, or protozoa that specify antigens important in stimulating the production of a protective immune response. Such comprehensive account of all aspects of the biology of all known species of orthopoxviruses will be valuable to molecular biologists, virologists, immunologists, pathologists, and researchers in the veterinary sciences.
The role of the cytokine, macrophage migration inhibitory factor (MIF), in the immune response and in the immunopathogenesis of different inflammatory, autoimmune, and infectious disorders is now well established. The aim of this handbook is to provide an authoritative volume covering all aspects of MIF, from basic molecular biology to structure-function relationships, pathophysiology, genetics, and drug development. Recent studies continue to broaden considerably the role of MIF in both normal physiology and pathology, which range from such diverse areas as oncogenesis, cardiac physiology, and neurodevelopment. MIF's molecular mechanism of action in these contexts is becoming increasingly understood and the role of variant MIF alleles in different conditions continues to be defined. Unique structural features of the protein, such as an intrinsic catalytic activity, and the continuing elucidation of its receptor-dependent mechanism of action offer attractive opportunities for therapeutic intervention. This volume will provide a comprehensive synthesis of the state of the art of MIF science.
Janeway's Immunobiology by Kenneth Murphy,Paul Travers,Mark Walport,Peter Walter Pdf
The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Tissue-specific stem cells have the capacity to self-renew and differentiate into several types of functional cells that replenish lost cells throughout an organism?s lifetime. Studies on stem cells from diverse systems have shown that stem cell function is controlled by extracellular cues from the niche and by intrinsic genetic programs within the stem cell. The objectives of this book would be to review the molecular mechanisms that mediate the balanced response of stem cells to the needs of the organisms. Likewise, niches have also been linked to pathologies, by imposing aberrant function on stem cells or other targets. Therefore, the second objective of this book would be to highligh the molecular dysregulation of niche biology leading to the disease. The third objective would be to review the therapeutical targets described within stem cell niches.
GPCR Signaling in Cancer, Volume 145, the latest release in the Advances in Cancer Research series, highlights recent developments in the area of GPCRs and cancer biology. Chapters included in this volume cover several GPCRs and their downstream effectors as case examples to highlight their fundamental understanding and therapeutic potential. Specific chapters address the Role of GRKs and beta-arrestins in cancer, Atypical GPCRs in cancer, the Role of a chemokine receptor (CCR) 5 in cancer, Targeting G protein-coupled receptors for therapeutics in cancer, Emerging GPCR signaling pathways in cancer, and more. G protein-coupled receptors (GPCRs) constitute a large family of cell surface receptors which are involved in nearly every cellular and physiological event. These receptors can recognize a broad array of ligands and they are targeted by nearly one third of the currently prescribed drugs including anti-cancer therapeutics. Covers the latest concepts in GPCR signaling and their relevancy to cancer biology Presents new indications for anti-cancer therapeutic programs Includes sections on cross-talk and signaling networks of GPCRs and effectors in molecular oncology and therapeutics
General Methods in Biomarker Research and their Applications by Victor R. Preedy,Vinood B. Patel Pdf
In the past decade there has been a major sea change in the way disease is diagnosed and investigated due to the advent of high throughput technologies, such as microarrays, lab on a chip, proteomics, genomics, lipomics, metabolomics etc. These advances have enabled the discovery of new and novel markers of disease relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders, sensory damage, intestinal diseases etc. In many instances these developments have gone hand in hand with the discovery of biomarkers elucidated via traditional or conventional methods, such as histopathology or clinical biochemistry. Together with microprocessor-based data analysis, advanced statistics and bioinformatics these markers have been used to identify individuals with active disease or pathology as well as those who are refractory or have distinguishing pathologies. New analytical methods that have been used to identify markers of disease and is suggested that there may be as many as 40 different platforms. Unfortunately techniques and methods have not been readily transferable to other disease states and sometimes diagnosis still relies on single analytes rather than a cohort of markers. There is thus a demand for a comprehensive and focused evidenced-based text and scientific literature that addresses these issues. Hence the formulation of Biomarkers in Disease. The series covers a wide number of areas including for example, nutrition, cancer, endocrinology, cardiology, addictions, immunology, birth defects, genetics and so on. The chapters are written by national or international experts and specialists.