Cytokines are soluble low-molecular weight glycoproteins or small polypeptides that act in an autocrine or paracrine manner between leukocytes and other cells. Cytokines have many biologic functions and are important for leukocyte growth and differentiation as well as activation and migration. Cytokines orchestrate defense, growth, fibrosis, angiogenesis, inflammation, and neoplasm control. They are synthesized by immunologic cells such as lymphocytes and monocytes/macrophages and by nonimmunologic cells such as keratinocytes and endothelial cells. Proinflammatory cytokines include interleukin-1 (IL-1), IL-2, interferon-? (IFN-?), and tumor necrosis factor-? (TNF-?), and antiinflammatory cytokines include IL-1 receptor antagonist, IL-4, IL-10, and transforming growth factor-? (TGF-?)4,5. The overexpression of inflammatory cytokines or decreased levels of antiinflammatory cytokines can lead to inflammatory cutaneous disorders. The CD4+ T-helper (Th) lymphocyte paradigm has also contributed to our understanding of inflammatory cutaneous disorders. CD4+ Th1 cells evoke cell-mediated immunity and phagocyte-dependent inflammation, while CD4+ Th2 cells evoke strong antibody, or humeral, immune responses, including those of the immunoglobulin E (IgE) antibody class, and inhibit phagocytosis.
[...] As our current knowledge of the immune system continues to grow, the application of safe and efficacious immunomodulators to treat these common skin conditions will continue to change and shape the field of dermatology. Conclusion Cytokines and chemokines are critical messengers of the immune system, as well as the homeostasis of peripheral tissues such as the skin. This class of molecules has been implicated in the pathogenesis of a number of dermatologic diseases. SUMMARY There has been a radical increase in our understanding of the pathogenesis of wound healing, scarring, skin cancer, and inflammatory dermatoses as well as improvements in their management and treatment. However, effective cures for these dermatologic conditions remain [...]
[...] When activated, these kinases phosphorylate cytoplasmic signal transduction proteins that bind to cis- acting elements and subsequently regulate cellular gene transcription rates. Fibroblast proliferation as well as collagen, fibronectin, and glycosaminoglycan production are decreased when IFNs bind to their receptors on fibroblasts. Interferon-α activates dermal fibroblast synthesis of collagenase and reduces the production of its natural inhibitor, tissue inhibitor of metalloproteinase-I (TIMP-I). In contrast, IFN-β has been shown to inhibit collagen production. Interferon-γ inhibits fibroblast proliferation, chemotaxis, and production of ECM macromolecules, including collagen and glycosaminoglycans. [...]
[...] Chemokines There are approximately 50 human chemokines that are classified into four families based on differences in their structure and function. The largest is the CC chemokine family. These chemokines have the first two of the four cysteine residues adjacent to each other; hence their name. These chemokines attract mononuclear cells to sites of chronic inflammation. The most widely studied CC chemokine is monocyte chemoattractant protein which is an important stimulator of monocytes, dendritic cells, and T cells. The second family of chemokines has been termed CXC, given that a single amino acid is interposed between first two of the four cysteine residues in each molecule. [...]
[...] and nonchemokine cytokines such as granulocyte-macrophage colonystimulating factor (GM-CSF)). The crystal structure of all chemokines share a disordered amino terminus, a β-pleaded sheet composed of three antiparallel strands, a carboxyl-terminal α-helix, and two to three disulfide bonds that stabilize the core of the protein12. Cytokines Transforming Growth Factor In the skin, TGF-β is produced by macrophages, fibroblasts, and epithelial cells, and has been shown to stimulate collagen gene expression and protein production. It has three isoforms in humans, and TGF-β signaling involves the interaction of at least three different receptors (types II, and III) through a heteromeric protein kinase receptor complex. [...]
[...] These cytokines have been designated as interleukins and newly discovered cytokines (or interleukins) are sequentially numbered. The number of interleukins is continuously growing, and it is currently up to IL-33110. However, cytokines with immunoregulatory properties such as GM-CSF have been omitted from this nomenclature system. Given the immunologic potency of interleukins and the role they play in the metabolism of the ECM, malignancy, and dermatologic inflammatory disorders, they have been targeted for the development of therapeutic applications. Interleukins not only regulate the metabolism of the ECM but also regulate fibroblast differentiation and proliferation. [...]
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