Sebum, inflammasomes and the skin: current concepts and future perspective.

Increasing evidence has identified ultraviolet radiation (UVR) as the skins most potent mutagen as over exposure results in sunburn, inflammation and DNA damage, thus contributing to a photo-ageing phenotype and possibly skin carcinogenesis. The lipid-rich sebum secreted onto the surface of the skin plays an important physiological role in protecting the skin against external challenges. When skin is photosensitised by UVR, the lipid constituents of sebum are easily oxidised, generating several lipid photo-oxidative products (e.g. squalene peroxides). These photo-oxidative products have been shown to exert diverse toxicological, biological and immunological effects in the skin and have therefore been implicated in several detrimental skin alterations including premature skin ageing. The involvement of lipid peroxidation products in UVR-induced inflammatory responses has been inadequately studied and highly controversial. Furthermore, it is unclear to what extent these oxidative products contribute to the underlying mechanisms of skin photo-ageing. Therefore, this viewpoint essay will discuss the current knowledge on the effect of UVR exposure on skin surface lipids and how these may mediate UVR-induced inflammatory responses which may be key contributors to photo-damage in skin. This essay will also examine the potential role of inflammasomes (innate immune complexes) in the inflammatory response associated with UVR-induced lipid peroxidation. Limited evidence is available on the interactions between sebaceous lipids, downstream mediators and concomitant immune response in sun-exposed skin and clearer elucidation may lead to novel biomarkers of photo-ageing and the incorporation of new molecules into current skin therapies which better target oxidised lipids and or downstream mediators/pathways.