COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE in Visual Studio .NET

Painting QR Code in Visual Studio .NET COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE

COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE
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Retinoids
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Retinoids, a class of vitamin A-derived compounds that bind various members of the retinoic acid receptor family, have long been used for the treatment of numerous inflammatory and hyperproliferative skin diseases Given the antiinflammatory nature of this class of compounds, retinoids are increasingly being used to counteract the effects of and prevent photoaging Among the numerous mechanisms of action characterizing these vitamin A derivatives, it was
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recently shown that the retinoids exert their anti-inflammatory effect through downregulation of TLR256 Because TLR2 has been implicated in the expression of MMPs, it is tempting to speculate that part of the mechanism of action of retinoids in photoaging is through the reduction of MMP expression via the downregulation of TLR2 Moreover, it has been well documented that retinoids directly affect MMP expression through negatively regulating AP-1 promoter activity,57 thereby displaying utility in reversing photoaging Retinoids have also been shown to increase TIMP expression, thus further promoting a matrix-preserving phenotype Retinoids are a common therapeutic agent for both the topical and systemic treatment of acne In addition to their antiproliferative effects, recent evidence has emerged to partially account for the anti-inflammatory effect The retinoid all-trans retinoic acid downregulates TLR2 and its coreceptor CD14 in monocytes Also, the addition of retinoids to culture media reduces proinflammatory cytokine production stimulated by P acnes56 MMPs have recently gained attention for their role in the pathogenesis of acne MMP-1, 3, and 9 have been shown to be markedly increased in lesional skin when compared to donormatched normal skin58,59 The overexpression of these MMPs may in part account for the scarring seen in acne It is possible that retinoids partially target MMP expression as part of their therapeutic mechanism Clinical evidence supports the role of retinoids in preventing scar formation and also for the treatment of both atrophic and hypertrophic scarring, perhaps indicating that retinoid regulation of MMPs may have important implications in the prevention and treatment of scarring60 62
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nism through the activation of various receptors including the TLRs can lead to cytokine alterations and have important implications in cellular apoptosis, inflammation, and tissue injury For example, the loss of TGF- or decreased responsiveness to EGF leads to a decrease in collagen production, as well as the increased breakdown of collagen and hyaluronic acid, accounting for the dermal alterations characteristic of photoaging A better understanding of the mechanisms of skin aging, and photoaging in particular, from an immunologic perspective should lead to the development of improved novel therapies Although currently there are no FDA-approved cytokine and growth factor therapies for photoaging, numerous cosmeceutical treatments containing these factors have been developed It is important to note that for those who practice evidencebased medicine, not enough data are available to know if these products reverse or prevent photoaging and further studies are warranted With the discovery of TLRs and their relationship to cytokine production as well as their indirect and direct links to collagen synthesis, it may be possible that TLRs could prove to be realistic targets for the prevention of photoaging Furthermore, therapeutics that directly target downstream events of TLR activation such as modulators of MMPs and TIMPs may be of use More research into the role of local immune response in skin aging should help provide physicians with tools to better treat and educate our patients
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1 Bell TV, Harley CB, Stetsko D, et al Expression of mRNA homologous to interleukin 1 in human epidermal cells J Invest Dermatol 1987;88:375 2 O Connor A, Nishigori C, Yarosh D, et al DNA double strand breaks in epidermal cells cause immune suppression in vivo and cytokine production in vitro J Immunol 1996;157:271 3 Kim J, Modlin RL, Moy RL, et al IL-10 production in cutaneous basal and squamous cell carcinomas A mechanism for evading the local T cell immune response J Immunol 1995;155:2240 4 Uyemura K, Castle SC, Makinodan T The frail elderly: role of dendritic cells in the susceptibility of infection Mech Ageing Dev 2002;123:955 5 Cohen S The stimulation of epidermal proliferation by a specific protein (EGF) Dev Biol 1965;12:394 6 Schultz GS, White M, Mitchell R, et al Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor Science 1987;235: 350
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