IMMUNOLOGY OF THE SKIN in Visual Studio .NET

Maker QR Code 2d barcode in Visual Studio .NET IMMUNOLOGY OF THE SKIN

CHAPTER 4 IMMUNOLOGY OF THE SKIN
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TABLE 4-2 Summary of Function of Cytokines and Growth Factors FUNCTION Cytokines Proin ammatory IL-1 ( , ) TNFIL-2 IL-4 IL-5 IL-6 IL-8 IL-12 Anti-in ammatory IL-10
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Keratinocyte differentiation, B cell differentiation, activates neutrophils and macrophages Similar to IL-1, prostaglandin synthesis in macrophages T-cell proliferation, cytokine production IgE production, mast cell and eosinophil maturation Eosinophil growth and differentiation Potentiates effects of TNF- and IL-1 Neutrophil chemoattractant Potentiates cell-mediated immunity Downregulates MHC class II, disrupts cytokine production, inhibits production of reactive oxygen species and NO
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Growth Factors TGFTGFEGF
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Enhances keratinocyte migration and keratinocyte differentiation Recruits monocytes, neutrophils, and broblasts, decreases matrix degradation Enhances keratinocyte migration and keratinocyte differentiation, accelerates wound healing, stimulates broblast migration and proliferation
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amphiregulin expression is downregulated in aged epidermis12 Diminished EGF activity and amphiregulin expression lead to a subsequent decrease in fibroblast migration and proliferation at the site of wound healing These events result in the impaired wound healing that is observed in aged skin Moreover, aged fibroblasts produce fewer matrix components,13 yielding less dermal tissue and a thinner, weaker scar Many cosmeceuticals now contain various growth factors including EGF, insulin-like growth factor, platelet growth factor, and keratinocyte growth factor Although these growth factors can theoretically induce keratinocyte differentiation and dermal remodeling, whether any of the products available to consumers demonstrate significant clinical effectiveness in preventing or reversing photoaging has not yet been established Since cosmeceuticals are not subject to the same FDA regulatory requirements as drugs, well-controlled clinical studies that support the efficacy of cosmeceuticals are generally not available The TGF- superfamily has a broad spectrum of functions dependent on the dosage and the target cell type In the wound healing process, TGFis responsible for recruiting monocytes, neutrophils, and fibroblasts to the wound site Higher concentrations of TGF- activate monocytes to release numerous growth factors and stimulate fibroblasts to increase matrix synthesis and decrease matrix degradation14 The effects of TGF- on keratinocytes are inconclusive with some studies showing an inhibitory role in growth, while others favoring keratinocyte chemoattraction and activation This apparent discrepancy is perhaps linked to the temporal kinetics, dose of TGF- administered, and also the dual activity TGFexerts on keratinocytes TGF- is best known in cosmetic dermatology for its ability to promote the production of the extracellular matrix, notably the synthesis of procollagen15 TGF- also serves as a growth factor for fibroblasts, the cells that produce collagen and play an important role in wound healing14 The subcutaneous injection of TGF- into unwounded skin results in increased collagen deposition at the injection site16 Moreover, collagen synthesis is enhanced in animal models when TGFis administered locally or systemically17,18 Despite the encouraging results of TGFon collagen synthesis, its effects on reepithelialization are less predictable In vivo studies have shown both accelerated and impaired reepithelialization in animal
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wound models,19,20 echoing the contradictory effects of TGF- on keratinocytes Loss of TGF- function may be significant in photoaging UV radiation impairs the TGF- pathway via downregulation of TGF- type II receptor (TGF- RII) Loss of TGF- RII occurs within 8 hours after irradiation and precedes the downregulation of type I procollagen expression,21 which leads to reduced collagen production Moreover, UV exposure decreases the expression of TGF- , and upregulates Smad7, a negative regulator of TGF22 For this reason, TGF- is included in skin care products Whether the TGF- and other growth factors contained in cosmeceuticals are stable, can be absorbed adequately, or exert a functionally significant outcome to induce dermal remodeling and reverse photoaging is unclear since well-controlled clinical studies are lacking
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in UVA-induced pigmentation in the epidermis26 Further studies are needed to clarify the role of UV-induced cytokines on melanocyte growth and function
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