The effects of UVB irradiance on aberrant epidermal proliferation: Novel insights on how to improve currently available sunscreens

Abstract

AimsSunscreen use, which prolonged the time required to develop sunburn by reducing the irradiance (mW/cm2) of the UVB radiation, is thought to protect the skin from developing cancers. Recently, in addition to fluence (mJ/cm2), irradiance of the UVB radiation was demonstrated to play an important role leading to photocarcinogenesis of the skin. After equivalent fluence of UVB exposure, enhanced aberrant keratinocyte proliferation contributes significantly to the photocarcinogenic capacity of low irradiance (LI) UVB as compared to its high irradiance (HI) UVB counterpart. However, the mechanism involved remains unclear. Main methodsRelevant cell and animal models were employed to investigate the effects of equivalent UVB fluence administered at HI or LI on keratinocyte proliferation. Additionally, the mechanisms involved were also explored. Key findingsWe found that at equivalent fluence, LIUVB induces significantly higher reactive oxidative species (ROS) production, cell proliferation, as well as phosphorylated AKT (pAKT) expression in both cell and animal models as compare to its HIUVB counterpart. Pretreating cultured keratinocytes with antioxidant or AKT inhibitor significantly reduced the UVB-induced ROS, cell proliferation, and pAKT expression. Additionally, these pretreatments abrogate the difference between the LI and HIUVB treated keratinocytes. Similar findings were noted using animal model treated with AKT inhibitor. SignificanceIn summary, at equivalent fluence, LIUVB induces significantly more aberrant epidermal proliferation via enhanced ROS and pAKT signaling. Reducing UVB-induced AKT phosphorylation presents a novel strategy to improve the protective capacity of the currently available sunscreens.