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Regulation of Chemokine- Receptor Interactions and Functions

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ISBN: 9783038427285 9783038427278 Year: Pages: 228 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biochemistry
Added to DOAB on : 2018-03-26 15:44:06
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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.

History of Chemoattractant Research

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197019 Year: Pages: 61 DOI: 10.3389/978-2-88919-701-9 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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In the Research Topic "History of Chemoattractant Research" we will portray some of the key discoveries that helped to transform cell migration research into a global playing field within immunology (and beyond). Early progress had a profound effect on both, academia and industry. Today, numerous academic laboratories are fully engaged in compiling a detailed road map describing the highly complex network of immune and tissue cells that respond to chemoattractants. Industrial research, on the other hand, centers on drugs that interfere with immune cell traffic in inflammatory diseases and cancer. The following series of “short stories” provide personal accounts on key discoveries. The individual molecular discoveries enabled numerous research laboratories worldwide to unravel their significance in steady-state or pathological immune processes. Although ground-breaking in their own right, it is therefore worth emphasizing that rapid progress in chemoattractant research was made possible by many other laboratories who were not directly involved in the original discovery process. Therefore, the authors of this mini-series are discussing their findings in the context of time, place and subsequent progress enabled by their discoveries. It is hoped that a wide readership will find these accounts entertaining as well as educational although those who wish to gain a more detailed knowledge are referred to the many outstanding reviews on chemokines and other chemoattractants.

The CXCR4 Ligand/Receptor Family and the DPP4 Protease in High-Risk Cardiovascular Patients

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198580 Year: Pages: 163 DOI: 10.3389/978-2-88919-858-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide, putting a major burden on life quality and social health care systems. Type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) have been identified as important risk factors for CVD, severely increasing the risk on e.g. myocardial infarction, and cardiovascular complications constitute the main cause of death in patients presenting with T2DM, CKD or a combination of both. As these pathologies are expected to rise alarmingly in the next decades, a better understanding of molecular and cellular mechanisms contributing to T2DM, CKD and CVD is required to improve prevention and treatment of these diseases. Furthermore, insight into the interplay between these pathologies and identification of molecular players interconnecting these comorbidities is of tremendous importance for optimal health management in the future. This Research Topic will focus on the chemokine receptor CXCR4 and its ligands CXCL12/SDF-1a and macrophage migration inhibitory factor (MIF) in the context of CVD and its link with T2DM and CKD, as well as address dipeptidyl peptidase-4 (DPP4) as an important protease destabilizing CXCL12. Chemokines and their receptors are important mediators of cell mobilization, recruitment and arrest, and also more broadly induce cell activation by triggering various intracellular signalling tracks. They control homeostatic conditions, but are also critically involved in inflammatory and pathological processes. Genome-wide association studies revealed single nucleotide polymorphisms connecting CXCL12 as well as MIF with CVD, and a role for both chemokines in T2DM and CKD has also been reported. In this review collection, current knowledge on molecular aspects of the CXCR4 ligand/receptor family and associated signalling pathways will be discussed. The physiological roles of CXCR4, CXCL12, MIF and DPP4 will be summarized, and recent findings on their function in pathological conditions of CVD, T2DM and CKD will be highlighted. This is combined with an extensive introduction providing insight into the pathologies of CVD, T2DM and CKD, discussing clinical features and common pathological aspects of these comorbidities on cellular and molecular level. Also, an overview of available animal models to study these diseases will be provided. This way, this Research Topic summarizes latest knowledge on this crucial molecular axis and its relationship with cardiovascular pathologies for both specialists and interested non-specialists and aims to stimulate further initiatives to unravel the mechanistic involvement of the CXCR4 ligand/receptor family in these morbidities, potentially paving the way for new therapeutical initiatives in the future.

Arrest chemokines

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194308 Year: Pages: 108 DOI: 10.3389/978-2-88919-430-8 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Arrest chemokines are a small group of chemokines that promote leukocyte arrest from rolling by triggering rapid integrin activation. Arrest chemokines have been described for neutrophils, monocytes, eosinophils, naïve lymphocytes and effector memory T cells. Most arrest chemokines are immobilized on the endothelial surface by binding to heparin sulfate proteoglycans. Whether soluble chemokines can promote integrin activation and arrest is controversial (Alon-Gerszten). Many aspects of the signaling pathway from the GPCR chemokine receptor to integrin activation are the subject of active investigation. Leukocyte adhesion deficiency III is a human disease in which chemokine-triggered integrin activation is defective because of a mutation in the cytoskeletal protein kindlin-3. About 10 different such mutations have been described. The defects seen in patients with LAD-III elucidate the importance of rapid integrin activation for host defense in humans. We welcome reports that help clarifying this crucial first step in the process of leukocyte transendothelial migration.

Chemokines and chemokine receptors in brain homeostasis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196166 Year: Pages: 124 DOI: 10.3389/978-2-88919-616-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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Virtually involved in all pathologies that present an inflammatory component, it is now evident that, in the central nervous system, chemokines and chemokine receptors possess pleiotropic properties beyond chemotaxis: costitutive brain expression of chemokines and their receptors on endothelial cells, but also on neurons and glia, suggests a role for such molecules in mediating homeostatic cross-talk between cells of the brain perenchyma. Cross-talk between neurons and glia is determinant to the establishment and maintenance of a brain enviroment that ensure normal function, and in particular glial cells are active players that respond to enviromental changes and act for the survival, growth, differentiation and repair of the nervous tissue: in this regard brain endogenous chemokines represent key molecules that play a role in brain development, neurogenesis, neurotransmission and neuroprotection. As important regulators of peripheral immune response, chemokines are molecules of the immune system that play a central role in coordinating communication between the nervous and the immune systems, in the context of infections and brain injury. Indeed, in phatological processes resulting from infections, brain trauma, ischemia and chronic neurodegenerative diseases, chemokines represent important neuroinflammatory mediators that drive leucocytes trafficking into the central nervous system, facilitating an immune response by targeting cells of the innate and adaptive immune system. The third edition of the international conference "Chemokines and Chemokine Receptors in the Nervous System", hold in Rome in October 2013, represented an exciting platform to promote discussion among researchers in different disciplines to understand the role of chemokines in brain homoestasis. This Frontiers Research Topic arises from this conference, and wants to be an opportunity to further discuss and highlight the importance of brain chemokines as key molecules that, not only grant the interplay between the immune and the nervous systems, but in addition drive modulatory functions on brain homeoastasis orchestrating neurons, microglia, and astrocytes communication.

Advances in Neuroimmunology

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ISBN: 9783038425700 9783038425717 Year: Pages: X, 150 DOI: 10.3390/books978-3-03842-571-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-12-06 12:41:40
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Neuroimmunity is a relative new and rapidly expanding area of interest that critically impacts normal brain function and a wide range of neurological disorders. Neuroimmune mechanisms operate within the nervous system and between the nervous system and periphery. Glial cells of the nervous system play a primary role in neuroimmunity, through their ability to produce and respond to neuroimmune signaling factors, which serve a number of functions, such as homeostatic regulation of nervous system function and defense against insult and infection. Dysfunction of the neuroimmune system is now thought to be an important contributing factor to many disease and injury states.The purpose of this Special Issue is to provide a representative view of current research in this growing field, with an emphasis on the central nervous system.

Mercury and Methylmercury Toxicology and Risk Assessment

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ISBN: 9783038979708 / 9783038979715 Year: Pages: 142 DOI: 10.3390/books978-3-03897-971-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Technology (General) --- Chemical Engineering
Added to DOAB on : 2019-06-26 08:44:06
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Mercury is a global pollutant that affects the health of both humans and ecosystems. This Special Issue collects three review papers and six research articles that report on the latest findings on the mechanisms of mercury toxicology and its impacts on environmental health. This collection of papers provides useful, new information on the mechanisms of mercury toxicity and methods of improving the risk assessment of mercury exposure.

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