Regulation of Chemokine- Receptor Interactions and Functions

Regulation of Chemokine- Receptor Interactions and Functions PDF

Author: Martin J. Stone (Ed.)

Publisher:

Published: 2018

Total Pages: 228

ISBN-13:

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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

Chemokines PDF

Author: Astrid E. Cardona

Publisher: Humana

Published: 2016-08-23

Total Pages: 0

ISBN-13: 9781493960057

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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.

Chemokine Receptors and NeuroAIDS

Chemokine Receptors and NeuroAIDS PDF

Author: Olimpia Meucci

Publisher: Springer Science & Business Media

Published: 2009-12-02

Total Pages: 446

ISBN-13: 1441907939

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Chemokine Receptors and NeuroAIDS: Beyond the Co-receptor Function and Links to Other Neuropathologies focuses on unresolved or emerging issues concerning the role of chemokine receptors in neuronal injury and HIV neuropathology, including their ability to regulate fundamental neuronal and glial functions and their role in neurovirulence and neurotoxicity. Although the importance of these molecules in the CNS physiology and pathology is now apparent, these issues are still matter of debate, and further research is required to design effective pharmacological agents that specifically target the brain chemokine system without major side effects. To this end, specific topics have been selected and are reviewed by international experts within the basic science/medical community. This book encourages investigation in the most controversial areas and fosters interaction between clinicians and basic scientists. The book also increases awareness about differences in disease progression among different parts of the world as well as selected patient populations, which may also help identifying novel therapeutic strategies.

Structural and Functional Analysis of Chemokine Interactions with Glycosaminoglycans and Chemokine Receptors

Structural and Functional Analysis of Chemokine Interactions with Glycosaminoglycans and Chemokine Receptors PDF

Author: Catherina L. Salanga

Publisher:

Published: 2011

Total Pages: 288

ISBN-13: 9781124703862

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Chemokines are involved in cell migration and activation during routine immune surveillance, inflammation and even cancer metastasis. The migration of chemokine receptor-bearing cells, including leukocytes and tumor cells, occurs in response to the secretion of chemokines, which accumulate on cell surfaces through interaction with glycosaminoglycans (GAGs) where they effectively serve as traffic signals to guide cell movement. Engagement of chemokines with their receptors subsequently causes the activation of signaling pathways that result in firm adhesion and extravasation of the cell into tissue, and in the case of leukocytes, activation of defense mechanisms. However, in cancer cells, the signaling pathways can be exploited or redirected, resulting in responses like survival, growth and proliferation. Herein, a structural and functional approach was used to address specific questions about the interactions of chemokines (i) with GAGs and (ii) with chemokine receptors in the context of cancer. Technically, the use of mass spectrometry has been a strong theme throughout these studies. In Chapter 2, a novel application of hydroxyl radical footprinting coupled with mass spectrometry was used to characterize the GAG binding specificity of the chemokine, MCP-3/CCL7. Potential GAG binding epitopes, identified by mass spectrometry, were then validated by mutagenesis and functional assays. In Chapter 3 and 4, a phosphoproteomic mass spectrometry strategy was used to elucidate CXCL12-mediated survival signaling through the receptor, CXCR4, in cells from patients with chronic lymphocytic leukemia (CLL). While signaling cascades involved in chemokine-mediated migration are well established, pathways involved in cell survival and proliferation in cancer, are not. Methods developed for phosphopeptide enrichment, and subsequent analysis via mass spectrometry are described in Chapter 3, and interesting/novel phosphoproteins, potentially involved in CXCL12-mediated CLL survival are described in Chapter 4. In Chapter 5, a functional approach was taken to elucidate the roles of receptors CXCR4 and CXCR7 in breast cancer growth and metastasis. The data show that CXCR7 affects the functional activity of CXCR4 in vitro, and decreases the extent of lung metastases in vivo, without inhibiting primary tumor growth. Overall, these studies serve to better understand some of the regulatory mechanisms that control chemokine function in normal physiology and in cancer.

Pathogen-Derived Immunomodulatory Molecules

Pathogen-Derived Immunomodulatory Molecules PDF

Author: Padraic G. Fallon

Publisher: Springer Science & Business Media

Published: 2010-05-30

Total Pages: 200

ISBN-13: 1441916016

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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.

The Chemokine Receptors

The Chemokine Receptors PDF

Author: Jeffrey K. Harrison

Publisher: Springer Science & Business Media

Published: 2007-11-17

Total Pages: 412

ISBN-13: 1597450200

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This volume, new to The Receptors series, focuses on several areas, including the birth, maturation, and structure of Chemokines; Neutrophil, Dendritic, and Lymphocyte trafficking; and Chemokine Receptors in diseases such as AIDs and lung cancer. In particular the book contains cutting-edge information ranging from basic molecular and cellular mechanisms to physiological and pathological roles of chemokines.

Sensory Nerves

Sensory Nerves PDF

Author: Brendan J. Canning

Publisher: Springer Science & Business Media

Published: 2009-08-05

Total Pages: 623

ISBN-13: 354079090X

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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.