640 CrispR/Cas9 deletion of TLR4 impacts the UV-induced stress response in human keratinocytes

Abstract

Several studies have shown that the ultraviolet (UVB/A) from terrestrial solar radiation are strongly implicated in the etiology of most skin cancers via the generation of DNA lesions and reactive oxygen species (ROS). Moreover, skin is also exposed to solar near infra-red (NIR) radiation which are responsible of oxidative stress generation. Therefore, it is important to protect the most sensitized skins (actinic keratosis or atopic dermatitis) in all circumstances/all day long. Thus, the aim of this project was to develop a SPF50+ sunfilter product in stick form to provide a nomad protection for sensitized skins. We demonstrated a very good genoprotection after an acute solar simulated irradiation in an in vitro reconstructed human epidermal (RHE) model with a very high protection of UV-induced cyclobutane pyrimidine dimers formation. Moreover, the quantification of ROS revealed that the topical application of sunscreen decreased significantly the free radical production in an ex vivo human skin model after acute UVA irradiation. In addition, the stick SPF50+ protection was evaluated on healthy subjects by the quantification of NIR-generated malondialdehyde (MDA), marker of lipid peroxidation. The topical application of the product decreased significantly the MDA production after NIR irradiation. Thus, the nomad sunfilter product provides an efficient protection against IR-generated oxidative stress. Finally, we showed that topical application of the sunscreen induced a physical barrier reinforcement on the RHE model by transepithelial electric resistance. Altogether, we demonstrated that the SPF50+ sunfilter stick shows a broad spectrum photoprotection not only UVB+A but also NIR, associated to a physical barrier reinforcement, providing a complete protection of the most sensitized skins.