Vitamin C prevents epidermal damage induced by PM-associated pollutants and UVA1 combined exposure.

Particulate matter is suspected to be substantially involved in pollution-induced health concerns. In fact, ultrafine particles (UFPs) contain polycyclic aromatic hydrocarbons (PAHs) known as mutagenic, cytotoxic and sometimes phototoxic. Since UFPs reach blood circulation from lung alveoli, deep skin is very likely contaminated by PAHs coming from either skin surface or blood. As photoreactive, benzo(a)pyrene (BaP) or indenopyrene (IcdP) is involved in the interplay between pollution and sunlight. In order to better characterize this process, experiments were carried out on reconstructed human epidermis (RHE) in a protocol mimicking realistic exposure. Concentrations of PAHs comparable to those generally reported in blood were used together with chronic irradiation to low dose UVA1. On a histological level, damaged cells mainly accumulated in a suprabasal situation, thus reducing living epidermis thickness. Stress markers such as IL1-α or MMP3 secretion increased, and surprisingly, the histological position of Transglutaminase-1 within epidermis was disturbed, whereas position of other differentiation markers (keratin-10, filaggrin, loricrin) remained unchanged. When vitamin C was added in culture medium, a very significant protection involving all markers was noticed. In conclusion, we provide here a model of interest to understand the epidermal deleterious consequences of pollution and to select efficient protective compounds.

Photo-pollution stress in skin: Traces of pollutants (PAH and particulate matter) impair redox homeostasis in keratinocytes exposed to UVA1.

BACKGROUND: It is likely that skin is exposed to low concentrations of pollutants such as Polycyclic Aromatic Hydrocarbons (PAH) either through topical penetration by ultrafine particles or by systemic distribution. No precise estimation of pollutants in living skin is available, but literature has reported contamination of blood by PAH at concentrations in the nanomolar range. Some pollutants (PAH for example) are photo-reactive and phototoxic: sunlight and pollution might thus synergistically compromise skin health. OBJECTIVE: Here, the biological effects of particulate matter, PM extract and various PAH were compared in normal human epidermal keratinocytes (NHEK) and reconstructed skin model exposed to either daily UV (d-UV 300-400nm) or UVA1 (350-400nm). Impact of pollutants (PM, PAH or PM extract) combined to UV was studied on NHEK by measuring toxicity, redox homeostasis and GSH metabolism in NHEK. METHODS: NHEK were exposed to UV from solar simulator (either d-UV or UVA1) combined with pollutants. Viability, clonogenic efficiency, redox homeostasis and GSH metabolism were assessed. RESULTS: Pollutants (PAH, PM or PM extract) ±UVA1 irradiation was associated with a significant phototoxic effect that was equal to or greater than that produced by d-UV. This result is interesting considering that UVA1 represents around 80% of daily UV and reaches the dermal-epidermal junction with ease. Moreover, among PAH studied, benzo[a]pyrene and indeno[1,2,3-cd]pyrene were phototoxic at very low concentrations (nanomolar range) on cultured cells or in reconstructed epidermis and also impaired keratinocyte clonogenic potential at sub-toxic doses. ROS generation within cells and in the inner mitochondrial compartment, mitochondrial membrane depolarization and/or reduced ATP production were also noted. Meanwhile, intracellular glutathione concentrations transiently decreased several hours post-treatment and reduction of its synthesis by buthionine sulfoximine potentiated PAH phototoxicity. Consequently, expression of GSH neo-synthesis genes such as SLC7A11 or GCLc was upregulated several hours post-treatment. CONCLUSION: These results obtained using PAH concentrations in the range of those reported in blood of pollution-exposed people suggest that exposure to such a photo-pollution stress, particularly if chronic, may impair cutaneous homeostasis and aggravate sunlight-induced skin damage.