Cytokine Growth Factor and Chemokine Ligand Database

unit 6.29

Cytokines and growth factors are widely used terms which describe a diverse group of soluble proteins and peptides that play a key role in the regulation of a number of physiological processes, including regulation of both innate and acquired immune responses to foreign and self-antigens, microbial pathogens, and cancer cells. These polypeptides, which include established cytokines and chemokines, and growth factors, including hormones and other soluble mediators, operate at extremely low concentrations to modulate the biological and molecular functions of cells, tissues, and/or entire organ systems. Cytokines and growth factors typically mediate interactions between cells via direct and indirect mechanisms regulating various immune and physiological processes. This regulation can occur either locally through cell-cell interactions within a specific tissue microenvironment or systemically via circulating cytokines in a fashion similar to that observed in hormone-mediated responses. The majority of these mediators are pleiotropic in their activities mediating various biological responses, both in vitro and in vivo. In addition, a number of cytokines and growth factors mediate overlapping effects on individual cell types yielding identical biological responses. Such overlapping activities may explain the lack of phenotypic changes in a factor-deficient host in that redundant mediators may compensate for certain deficiencies. Cytokine and growth factor expression are strictly regulated in that only cells in response to an inflammatory or activation signal produce many of these factors. Protein and RNA expression is usually transient and can be regulated at various stages of gene expression and translation. The expression of many these mediators also seem to be regulated differentially, depending on cell type, developmental stage, and age. Moreover, many of these factors have also been shown to play critical roles in a variety of pathophysiological processes including sepsis, asthma, allergy, contact sensitivity, various forms of hypersensitivity, acute phase reactions, wound healing, coagulation, embryogenesis, organ development, angiogenesis, and a variety of CNS functions. Cytokines and growth factors also important regulators of cell division, differentiation, chemotaxis and adhesion, cellular trafficking, cell activation, apoptosis, cell survival, and transformation. Thus, the development of antagonists to cytokine mediators is an incredibly hot topic, with many labs and companies studying various forms of inflammation and inflammatory diseases, and their control. In addition, given the potent and selective properties of certain cytokines, individual cytokines have also been utilized for therapeutic interventions into various immunodeficient and neoplastic disease states, tissue transplantation, and hematopoietic dysfunction.

This unit describes specific features of a given cytokine, growth factor, or chemokine, including alternative nomenclature listings for each mediator, biochemical and molecular characteristics, regulation of expression, biological and physiological functions, observations in transgenic and knockout animal models, pathophysiological associations, and potential clinical applications (Table 6.29.1).

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