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AUTORES : Belaidi Jean-Philippe Chollet Christel Denat Laurence Dimitrov Ariane Eilstein Joan Erdmann Dominique Jones Christophe Lereaux Guillaume Lereaux Guillaume- Marrot L Mezzache Sakina Perez Philippe Soeur Jeremie Zanini Martine Zobiri Olivia

MODELOS : RHE / RECONSTRUCTED HUMAN EPIDERMIS

APLICAÇÕES : UVA / UVB

2017 Journal of Dermatological Science 86 (2017) 162–169
L'Oreal

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 PolycyclicAromatic Hydrocarbons (PAH) either through topical penetration by ultrafine particles or by systemicdistribution. No precise estimation of pollutants in living skin is available, but literature has reportedcontamination of blood by PAH at concentrations in the nanomolar range. Some pollutants (PAH forexample) are photo-reactive and phototoxic: sunlight and pollution might thus synergisticallycompromise skin health.

 Objective: Here, the biological effects of particulate matter, PM extract and various PAH were compared innormal human epidermal keratinocytes (NHEK) and reconstructed skin model exposed to either daily UV(d-UV 300–400 nm) or UVA1 (350–400 nm). Impact of pollutants (PM, PAH or PM extract) combined toUV 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 withpollutants. Viability, clonogenic efficiency, redox homeostasis and GSH metabolism were assessed.

Results: Pollutants (PAH, PM or PM extract)UVA1 irradiation was associated with a significantphototoxic effect that was equal to or greater than that produced by d-UV. This result is interestingconsidering that UVA1 represents around 80% of daily UV and reaches the dermal-epidermal junctionwith ease. Moreover, among PAH studied, benzo[a]pyrene and indeno[1,2,3-cd]pyrene were phototoxicat very low concentrations (nanomolar range) on cultured cells or in reconstructed epidermis and alsoimpaired keratinocyte clonogenic potential at sub-toxic doses. ROS generation within cells and in theinner mitochondrial compartment, mitochondrial membrane depolarization and/or reduced ATPproduction were also noted. Meanwhile, intracellular glutathione concentrations transiently decreasedseveral hours post-treatment and reduction of its synthesis by buthionine sulfoximine potentiated PAHphototoxicity. Consequently, expression of GSH neo-synthesis genes such as SLC7A11 or GCLc wasupregulated several hours post-treatment.

Conclusion: These results obtained using PAH concentrations in the range of those reported in blood ofpollution-exposed people suggest that exposure to such a photo-pollution stress, particularly if chronic,may impair cutaneous homeostasis and aggravate sunlight-induced skin damage.© 2017 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.