Involvement of nuclear factor of activated T cells activation in UV response - Evidence from cell culture and transgenic mice

Mammalian cells respond to UV radiation by signaling cascades leading to ac tivation of transcription factors, such as activated protein 1, NF kappa B, and p53, a process known as the "UV response." Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immu ne response and subsequently found to be expressed in other tissues and cel ls. To date, however, the regulation and function of NFAT in tissues and ce lls, other than the immune system, are not well understood. In this study, we demonstrate that UV radiation activates NEAT-dependent transcription thr ough a calcium-dependent mechanism in mouse epidermal JB6 cell lines, as we ll as in the skin of NFAT-luciferase reporter transgenic mice. Exposure of JB6 cells to UV radiation leads to the transactivation of NEAT in a dose-de pendent manner. A23187 had a synergistic effect with UV for NFAT induction, whereas pretreatment of cells with nifedipine, a calcium channel blocker, dramatically impaired the NFAT activity induced by either UV or UV plus A23 187, Calcium-dependent activation of NEAT by UV was further confirmed by an in vivo study using NFAT-luciferase reporter transgenic mice. These result s demonstrated that UV radiation is a strong activator for skin NFAT transa ctivation through calcium-dependent pathways, suggesting that NEAT activati on may be a part of the UV response.