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.

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

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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 guides the reader through the latest research on the cytokine network, covering signaling pathways, control of the immune response, and potential therapeutics. Different cytokines stimulate diverse responses in various phases of inflammation and immunity, including the innate immune response, the generation of effector T cells, and the development of antibodies by the humoral immune system. It is now clear that the pathophysiology of many infectious, autoimmune, allergic, and malignant diseases can be largely explained by which cytokines are induced and subsequently regulate the cellular responses. In clinical medicine, cytokines are involved in a wide spectrum of diseases. This book describes in three parts the properties and roles of 15 key cytokines under physiological and pathological conditions. Part I presents nine cytokines associated with inflammatory disorders, pro-inflammatory cytokines, and the recently identified new helper T (Th) subset: Th17 cells. Part II gives details of three cytokines associated with allergic disorders, including Th2 responses and recently identified types of innate cells. Part III describes three cytokines that are associated with immunological tolerance and anti-inflammation, including regulatory T (Treg) cells, IL-10-producing Treg (Tr1) cells, and inducible IL-35-producing Treg (iTr35) cells. Cytokines are considered to be important as therapeutic targets for specific agonists or antagonists in numerous immune and inflammatory diseases. The ultimate goal of this book is to facilitate the development of therapeutic treatments for such diseases which has been limited by an insufficient understanding of the biology of cytokines and the complicated network that they create.

In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular signaling web operates properly in health and improperly in disease. The stability of the health- and disease-associated states is dynamic and supported by multiple feedback loops acting positively and negatively along with linkages between pathways. During the past few years an ongoing series of important discoveries have been made that advance our understanding of how the body works and may guide us on how to better deal with these diseases. These include the discovery of chronic inflammation as a causal factor in all of these disease classes, the appearance of reactive oxygen species as a messenger molecule that can act both positively and negatively, the propensity of proteins to misfold into aggregation- and disease-prone forms, and the rise of epigenetics including the emergence of small non-coding RNA with important regulatory functions out of the so-called junk RNA. Chapters are devoted to each of these classes of findings with additional details integrated into the chapters dealing directly with the diseases. The connections responsible for maintaining stability are explored in depth.