Modulation of Gene Expression Induced in Human Epidermis by Environmental Stress In Vivo

Abstract

Environmental insults on the skin induce biologic responses through the modulation of expression of genes implicated in different cell functions. The aim of this study was to investigate the modulation of gene expression profile in human epidermis in vivo following different stresses. We determined the modulations of gene expression using cDNA macroarray in the epidermis of 28 healthy volunteers, following mild and physiologic insults, including: (1), tape stripping; (2) application of 10% sodium dodecyl sulfate; (3) daily application of vaseline; and (4), exposure to one minimal erythema dose of solar-simulated radiation. The analysis was performed 19 h after treatment. The reverse transcription-polymerase chain reaction method was used to confirm our results. We showed that: (1) the intensity of gene modulation was variable among the volunteers following the same skin stress; (2) the nature and intensity of skin treatment modified the pattern of gene expression; and (3) some genes were modulated only by specific stress, some others are modulated irrespective of the stress. GADD45, Bax, SAS, and granulocyte chemotactic protein-2 were overexpressed exclusively following solar-simulated radiation, whereas tape stripping led to the modulation of genes implicated in different pathways (inflammation, cell proliferation, cell differentiation, detoxification, etc.). Concerning common gene modulation, MRP8 and MRP14 were highly upregulated in human skin epidermis after solar-simulated radiation, vaseline application or tape stripping, and to a lower extent after sodium dodecyl sulfate. Such upregulation of the MRP 8/14 genes was confirmed at the protein level in an ex-vivo skin culture model following tape stripping and solar-simulated radiation. Together, these results suggest that MRP8 and MRP14 may be general, yet highly sensitive, markers for a great variety of skin stresses and that they are implicated in several epidermal repair pathways.

Human Keratinocytes' Response to Injury Upregulates CCL20 and Other Genes Linking Innate and Adaptive Immunity

“…Genes related to innate immunity were also upregulated in sorted KCs, including members of the S100 family of proteins (S100A7, S100A8, S100A9) and other AMPs (RNASE7, NGAL, elafin). With the exception of RNASE7, these AMPs have also been identified in other wound healing studies (Marionnet et al , 2003; Roupe et al , 2010; Sorensen et al , 2006). Upregulated cytokines/chemokines (IL-1α, IL-8, TNF, IFN-κ, and CXCL1), with the exception of IFN-κ, are also consistent with other wound healing studies (Dickel et al , 2010; Marionnet et al , 2003; Nickoloff and Naidu, 1994; Roupe et al , 2010).…”

“…Current evidence largely links KCs to activation of pathways that direct innate immune responses, e.g., neutrophil recruitment into sites of injured epidermis (Marionnet et al , 2003; Roupe et al , 2010; Sextius et al , 2010); however, more research is needed to define the isolated response of KCs to injury, including their potential to recruit and activate cells of adaptive immunity.…”

“…Prior in vivo wound healing studies have attempted to define the epidermal response to injury, however, it was unclear what role was played by dermally-derived cells such as fibroblasts and inflammatory cells (Cole et al , 2001; Dickel et al , 2010; Johnston et al , 2010; Marionnet et al , 2003; Nickoloff and Naidu, 1994; Roupe et al , 2010; Sextius et al , 2010). In vitro studies using cultured KCs and three dimensional skin equivalents have the advantage of a system populated solely by KCs (Dayem et al , 2003; Koria et al , 2003), but these cell models are intrinsically growth-activated and have a different gene expression profile from normal skin (Gazel et al , 2003).…”

Melanocyte and Melanoma Cell Activation by Calprotectin

“…Calprotectin exerts its effects by binding to a variety of receptors on the surface of target cells, including Toll-like receptor 4 (TLR4), the receptor for advanced glycation end-products (RAGE), and extracellular matrix metalloproteinase inducer (EMMPRIN) [5–7]. S100A8 and A9 are expressed at extremely low levels in unperturbed keratinocytes, but their expression is readily stimulated by a variety of insults, including UVR exposure [8]. Calprotectin is chemotactic for leukocytes and keratinocytes; thus, it stimulates keratinocyte motility and recruits inflammatory cells to the skin [9].…”

Characterization of molecules showing altered expression profile in psoriasis

“…Mechanical stress causing disruption of the skin barrier leads to molecular responses, including a rapid increase in DNA synthesis and early over-expression of pro-inflammatory cytokines (Marionnet et al, 2003;Wood et al, 1997). It has long been known that baseline proliferative activity of keratinocytes of non-involved skin of psoriatic patients does not differ from keratinocytes in skin of healthy individuals; however, the proliferative response to TS or other trauma is significantly higher in psoriatic non-involved skin compared to healthy skin (Hatta et al, 1997;van de Kerkhof et al, 1983;Wiley and Weinstein, 1979).…”