Keratinocyte-derived tumor necrosis factor-alpha (TNF-a) contributes to more epidermal proliferation induced by UVB exposure at low-irradiance: Novel insights on improving currently available sunscreens.

Summary: Abstract Body: The skin exhibits erythema upon exposure to a specific threshold of UVB fluence (mJ/cm2). Sunscreen application, which extends the duration required for erythema to develop by reducing the irradiance (mW/cm2) of UVB radiation, is believed to offer protection against the development of skin cancers. Recent studies have highlighted the significant role of UVB irradiance, in addition to fluence, in skin photocarcinogenesis. Following exposure to an equivalent UVB fluence, increased aberrant keratinocyte proliferation has been shown to significantly contribute to the photocarcinogenic potential of low irradiance (LI) UVB compared to its high irradiance (HI) counterpart. However, the underlying mechanisms remain unclear. In this study, we examined the effects of equivalent UVB fluence administered at either HI or LI on epidermal keratinocytes. Our findings demonstrated that, at equivalent fluence, LIUVB induces significantly greater cell proliferation, TNF-a production, and phosphorylated AKT (pAKT) expression in both cellular and animal models compared to HIUVB. UVB-induced AKT signaling played a critical role in the increased cell proliferation. Furthermore, pretreatment with TNF-a inhibitors effectively eliminated the differences in cell proliferation and pAKT expression between HI and LIUVB in both cellular and animal models. In conclusion, compared to its HI counterpart, LIUVB, at equivalent fluence, induces significantly greater aberrant epidermal proliferation through enhanced TNF-a production. Incorporating agents that modulate TNF-a inhibition into sunscreens may improve their efficacy in protecting the skin from UVB-induced damage. Cheng-Che Lan², Shu-Mei Huang¹, Yu-Ting Peng¹, Ting-Ting Yang² 1. Dermatology, Kaohsiung Medical University and Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 2. Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. UV Biology/Injury and Non-melanoma Cancers