602 Discovery of new olfactory receptors in human keratinocytes: A potential role on skin stress response

Olfactory receptors (ORs) are mainly expressed in the nasal olfactory epithelium but can also be found in different cell types throughout the body to regulate physiological cell functions beyond olfaction. Recently, ORs have been detected to be functionally expressed in the skin when activated with odorants. Olfaction is known to be disturbed under stress condition and is widely used in aromachology to afford relaxing effect. Therefore, we questioned the role of skin olfactory receptors in response to this environmental factor. For the first time, we showed the presence of OR10A6, OR2AG2 and OR11H4 in human primary keratinocytes cells and on human skin.n ex-vivo skin model stressed with high levels of epinephrine, a stress hormone, during 9 days was developed. In addition to an acceleration of the cell activity and perturbation of DNA repair with a significant increase of Loricrin, G6pDH and gH2AX of respectively +132%, +27% and +71% (p<0.05), we observed by qPCR and immunofluorescence a decrease of the expression of the 3 ORs (p<0.001) compared to control. Identification of phenylethyl alcohol (PEA) and a PEA-rich rose extract as an agonist of these receptors was realized on cloned ORs. These agonists allowed to protect the skin against the impact of stress but also to restore ORs level of expression, especially for OR2AG2. Overall, these finding suggest that OR10A6, OR2AG2 and OR11H4 are involved into stress response mechanisms and demonstrate that olfactory receptors activation may serve as a new target to fight skin stress.