Détails de la réservation
- Le : 4 July 2017
- De : 14 h 00
- à : 15 h 30
- Salle : Salle de conférence
Détails de l'évènement
Jean Krutmann
“The AHR as a sensor of environmental stress to skin”
Résumé
Chronic exposure to solar radiation is a major cause of environmentally-induced skin aging, which is therefore traditionally referred to as photoaging. We and others have shown that within the solar spectrum, wavelengths in the Ultraviolet (UV) B and A range, but also visible light and near infrared radiation can cause skin aging (reviewed in 1). More recent studies suggest, however, that extrinsic skin aging is more than photoaging and, in particular, that traffic related air pollution independently contributes to skin aging. In epidemiological studies chronic exposure to ambient particulate matter (PM) as well as nitrogen oxide (NO2) was found to be significantly associated with more pigment spots on cheeks of elderly Caucasian as well as Han Chinese (2,3). This association was modified by genetic variants. Accordingly, we observed a significant interaction between air pollution and Arylhydrocarbon Receptor (AHR) /Arylhyrocarbon Receptor Repressor genetic risk scores on cheek lentigines. Women with a high genetic risk score for AHR/AHRR develop 52 % more lentigines on the cheeks after an increase of 4.45 μg/m3 (IQR) in PM2.5 and 36 % more lentigines after an increase of 5.54 μg/m3 (IQR) in PM10, whereas there was no association in women with a low risk score. We thus show that gene environment interactions are involved in environmentally-induced skin aging in general and air pollution-induced lentigines formation in particular. These results also indicate that AHR signaling is involved in environmentally-induced skin aging. In line with this assumption are in vitro studies in which topical application of ambient relevant Diesel Exhaust Particles caused AHR-dependent gene transcription in ex vivo human skin models. Interestingly, AHR signaling may also be induced in skin by UVB irradiation (4) and critically contribute to photocarcinogenesis. In contrast to AHR +/+ mice, AHR -/- animals developed 50 % less skin tumors in a chronic UVB irradiation study. In subsequent experiments we found that this procarcinogenic action of AHR signaling is due to a negative regulation of DNA damage responses in UVB irradiated keratinocytes which critically involves the interaction of AHR with p27 (5). Taken together these studies suggest that AHR might be a molecular target for the prevention of extrinsic skin aging / skin cancer (6). We have therefore recently developed a competitive AHR antagonist which can be topically applied to human skin and inhibit UVB radiation as well as air pollution-induced AHR activation in human skin cells in vitro and in vivo (7).
Invitation : Alain Taïeb – Inserm U 1035
Responsable
- Nom : Rocher Virginie