Effects of all-trans retinoic acid on UVB-irradiated human skin substitute

Abstract

Retinoids are frequently used for treatment of photodamaged skin. We wished to find out whether photodamage could be attenuated by applying all-trans retinoic acid (RA) during repetitive irradiation. For this purpose, we used human cutaneous cells and tissue: pure monolayer cultures containing either keratinocytes or fibroblasts, and human skin substitute (SS) containing both cell types. All cultures were exposed to 8 mJ/cm(2) of UVB and were immediately treated with RA (0, 1.5, or 3 microM). The irradiation and RA treatment protocol was repeated until the cells of the nonirradiated culture had reached confluence. In the irradiated SS, RA preserved the structure (epidermal stratification and differentiation) and ultrastructure (well-organized intermediate filaments and desmosomes) in a state comparable to that observed in nonirradiated SS. As well RA maintained secretion of basement membrane components (laminin and type-IV collagen). Following irradiation, cutaneous cells also displayed more proliferative capacity when SS was treated. In the irradiated monolayer cultures, RA maintained the proliferative capacity of fibroblasts and decreased their differentiation whereas the opposite effect was seen on keratinocytes. In conclusion, RA clearly helps protect human skin against photodamage induced by repeated exposure to UVB.

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

“…To that end, several pharmacologic strategies have been explored to regulate desmosome stability in epidermal cells. Treatment of organotypic epidermal models with retinoic acid results in normalization of desmosome appearance after a low dose of UVB exposure (Chouinard and Rouabhia 1999) but retinoic acid is more frequently reported to down-regulate expression of desmosomal components in human skin (Humphries et al 1998;Wanner et al 1999;Kim et al 2011). A serine palmitoyltransferase inhibitor (ISP-I) increases the number of corneodesmosomes leading to a thicker stratum corneum and less transepidermal water loss (Mizukoshi et al 2011).…”

Cytokine Release and Cytotoxicity in Human Keratinocytes Induced by Polycyclic Aromatic Hydrocarbons (1-Methylpyrene and Perylene)

“…Culture medium was refreshed every 48 h with new medium containing the appropriate PAH concentration. On d 9, the colonies were fixed for 30 min with 10% formaldehyde in PBS, rinsed, and stained with 1% rhodanile blue (Chouinard & Rouabhia, 1999). At this culture period, no irradiated mouse 3T3 fibroblasts remained present in the culture.…”

The effects of epigallocatechin-3-gallate on extracellular matrix metabolism

“…EGCG and RA were added into KBM or DMEM for 24 h at concentrations of 0.01 and 0.1 mM, which were selected based upon our prior studies and experiences [23,24]. For the AS, EGCG or RA concentrations were determined according to those of commercially marketed cosmetics and previous reports [10,11]. The 2% EGCG and 0.01% RA was prepared, diluted in propylene glycol and ethanol (at the ratio of 3:7).…”

“…Retinoids are known to induce the proliferation of keratinocytes and fibroblasts, to promote collagen synthesis and to decrease the MMPs expression level in the dermis [8][9][10]. Moreover, the molecular mechanisms of how retinoids suppress the MMP-1 expression induced by UV are well known [2,6,10].…”

“…Moreover, the molecular mechanisms of how retinoids suppress the MMP-1 expression induced by UV are well known [2,6,10]. Therefore, retinoids are widely used as topical agents for improving the skin damage induced by UV radiation [2,3].…”