In recent years, powered by evolving technologies and experimental design, studies have better illuminated the regulating role of proteolytic enzymes across human development and pathologies. Proteolytic Signaling in Health and Disease provides an in-depth discussion of fundamental physiological and developmental processes regulated by proteases, from protein turnover and autophagy to antigen processing and presentation and major histocompatibility complex (MHC) molecules. Moving on from basic biology, international chapter authors examine a range of pathological conditions associated with proteolysis, including inflammation, wound healing, and cancer. Later chapters discuss the newly discovered network of connected events among proteases (and their inhibitors), the so-called 'protease web', and how best to study it. This book also empowers new research with up-to-date analytical methods and step-by-step protocols for studying proteolytic signaling events. - Examines biological events triggered by proteolytic enzyme activity across human development and pathologies - Discusses the role of proteolytic signaling in inflammation, wound healing, and cancer, among other disease types - Features methods and protocols supporting further study of proteolytic signaling events - Includes chapter contributions from international leaders in the field

This timely volume provides a comprehensive overview of glucocorticoids and their role in regulating many aspects of physiology and their use in the treatment of disease. The book is broken into four sections that begin by giving a general introduction to glucocorticoids and a brief history of the field. The second section will discuss the effects of glucocorticoids on metabolism, while the third section will cover the effects of glucocorticoids on key tissues. The final section will discuss general topics, such as animal models in glucocorticoid research and clinical implications of glucocorticoid research. Featuring chapters from leaders in the field, this volume will be of interest to both researchers and clinicians.

This book discusses recent research in innate immunity, which has revealed a large number of receptors that sense the presence of microorganisms or cellular damage in tissues. In complex tissues, many of these sensing events occur simultaneously. Thus, the downstream signaling pathways need to be integrated so that an appropriate cellular inflammatory response can be initiated. In addition, the inflammasome defines the molecular and cellular processes of inflammation in response to microbial infection. Previous data suggested that regulation of inflammasomes is mediated by microbes, but inflammasomes also have antimicrobial functions. Increasing evidence in mouse models, together with human data, strongly implicates an involvement of the inflammasome and uncontrolled inflammation in the initiation and progression of diseases with a high impact on public health. The book reviews novel aspects of functional genomics, epigenomics, transcriptomics, post-translat ional modifications, microbiome and immunometabolism in order to understand inflammatory signaling and responses, covering recent findings on the mechanisms underlying the regulation of inflammatory responses to pathogens, dysregulation of these responses in inflammatory disease, and the use of such mechanisms to boost or subdue the inflammatory response. Bridging the gaps in understanding between the fields of human and mouse immunology, it provides valuable insights into inflammatory-mediated disease and immune defense. Such innovative perspectives in both basic and clinical research promote the translation of knowledge to the clinic.

The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

This book highlights the important role free fatty acids (FFA) play as potential drug targets. While FFA have long been considered byproducts of cell metabolism, they are now recognized as ligands that regulate cell and tissue function via G-protein-coupled receptors. At least three receptors have been identified for which FFA appear to be the endogenous ligands.

This book provides readers with an up-to-date and comprehensive view on the resolution of inflammation and on new developments in this area, including pro-resolution mediators, apoptosis, macrophage clearance of apoptotic cells, possible novel drug developments.