A broad-spectrum sunscreen prevents UVA radiation-induced gene expression in reconstructed skin in vitro and in human skin in vivo

Abstract

The efficacy of sunscreens to protect against ultraviolet (UV) A radiation is usually assessed by measuring erythema formation and pigmentation. The biological relevance of these endpoints for UVA-induced skin damage, however, is not known. We therefore carried out two complementary studies to determine UVA protection provided by a broad-spectrum sunscreen product at a molecular level by studying UVA radiation-induced gene expression. One study was performed on human reconstructed skin in vitro with a semi-global gene expression analysis of 227 genes in fibroblasts and 244 in keratinocytes. The second one was conducted in vivo in human volunteers and focused on genes involved in oxidative stress response and photo-ageing (haeme oxygenase-1, superoxide dismutase-2, glutathione peroxidase, catalase, matrix metalloproteinase-1). In-vitro UVA radiation induced modulation of genes involved in extracellular matrix homeostasis, oxidative stress, heat shock responses, cell growth, inflammation and epidermal differentiation. Sunscreen pre-application abrogated or significantly reduced these effects, as underlined by unsupervised clustering analysis. The in vivo study confirmed that the sunscreen prevented UVA radiation-induced transcriptional expression of the five studied genes. These findings indicate the high efficacy of a broad-spectrum sunscreen in protecting human skin against UVA-induced gene responses and suggest that this approach is a biologically relevant complement to existing methods.

Diversity of Biological Effects Induced by Longwave UVA Rays (UVA1) in Reconstructed Skin

“…We previously showed that UVA spectrum, including UVA2 and UVA1, can induce proinflammatory mediators in reconstructed skin [19]. We now show that UVA1 exposure per se induced an increase in the level of inflammation markers, such as IL6, CCL20 and CSF2 (GM-CSF) genes and proteins as well as IL1A, IL1B, IL8, PTGS2 (COX-2), TNFAIP3, ICAM1 and LIF genes.…”

“…The three dimensional architecture of the model allows us to take into account UV penetration properties depending on wavelength [16]. Using this model, we have previously reproduced the major epidermal alterations induced by UVB as well as identified direct dermal damage occurring after UVA (including UVA2 and UVA1) through ROS generation, dermal fibroblast apoptosis, matrix metalloproteinase (MMP) release and modulation of the expression of genes related to extracellular matrix homeostasis [17]–[19].…”

Biological contribution of UVA wavelengths in non extreme daily UV exposure

“…Meanwhile, 3 major proteins involved in ECM remodeling were significantly induced: 2 matrix metalloproteinases, MMP1 and MMP3 and SERPINB2, one of the major inhibitor of the Plasminogen Activator system. The modulation of these markers following UVA exposure has previously been described [5,6]. We report that, even very low doses of DUVR can also affect the expression of genes that encode proteins involved in ECM composition, maturation and remodeling, that occurs during photoaging process.…”

Solar ultraviolet radiation induces biological alterations in human skin in vitro: Relevance of a well-balanced UVA/UVB protection

“…Sunscreen pre-application abrogated these effects or reduced them significantly. This revealed a very high photoprotective activity of the sunscreen that could be evidenced using an unsupervised clustering analysis or a gene by gene comparison approach [40] [ Figure 6]. This data indicated that a broad-spectrum sunscreen Figure 6: Heat map of gene expression in reconstructed skin exposed to 30 J/cm 2 UVA.…”

“…[37][38][39][40] Since the in vitro model has a horny layer, it is possible to apply the products topically on skin surface, thus mimicking real life conditions. The protecting effects against UV-induced epidermal or dermal damage in reconstructed skin model can be evaluated at various time points after exposure.…”