IN-VITRO MECHANISM(S) OF ULTRAVIOLET-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA RELEASE IN A HUMAN KERATINOCYTE CELL-LINE

It has been demonstrated that ultraviolet (UV) irradiation is able to induce both in vivo and in vitro, tumor necrosis factor-alpha (TNF) re lease. The purpose of the present study was to evaluate, using a human keratinocyte cell line NCTC 2544, the mechanism(s) of UV-induced TNF release and the ability of commonly used sunscreens to modulate UV-ind uced TNF release. TNF release can be partially prevented both by addin g an anti-human IL-1 alpha antibody after irradiation, suggesting an a utocrine effect of IL-1 alpha in inducing TNF release, and by adding a ntioxidants indicating also a role of oxidant species. TPCK, a I kappa -B alpha protease inhibitor, was able to virtually abolish UV-induced TNF release, indicating that UV-induced TNF release requires NF-kappa B activation. Anti-human IL-1 beta antibody was ineffective as expecte d, considering that keratinocytes are unable to process pre-IL-1 beta to its active form. To evaluate the sunscreen's modulation on UV-induc ed TNF release, confluent cells were irradiated, in the presence or ab sence of the tested sunscreens (Uvinul MS40, Uvinul P25 and Uvinul DS4 9). Different IC50 values could be calculated, which may be related to different UV absorption spectrums: Uvinul MS40 offers great protectio n by virtue of its broader absorption spectrum, closely followed by Uv inul P25 and finally by Uvinul DS49.