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.


CONCLUSIONS
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.
L'Oréal Research & Innovation, Aulnay sous Bois, France. Electronic address: jsoeur@rd.loreal.com.
Jérémie
J
Soeur
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Jean-Philippe
JP
Belaïdi
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Christel
C
Chollet
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Laurence
L
Denat
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Ariane
A
Dimitrov
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Christophe
C
Jones
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Philippe
P
Perez
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Martine
M
Zanini
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Olivia
O
Zobiri
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Sakina
S
Mezzache
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Dominique
D
Erdmann
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Guillaume
G
Lereaux
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Joan
J
Eilstein
L'Oréal Research & Innovation, Aulnay sous Bois, France.
Laurent
L
Marrot
D000393:Air Pollutants / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival; D004817:Epidermis / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000528:radiation effects; D008027:Light; D053078:Membrane Potential, Mitochondrial; D010084:Oxidation-Reduction; D052638:Particulate Matter / Q000633:toxicity*; D010777:Photochemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D013472:Sunlight; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000393:Air Pollutants; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D005978:Glutathione
Glutathione; Hydrocarbons; Keratinocyte; Particulate matter; Pollution; Polycyclic aromatic; Redox homeostasis; Uva