POSSIBLE ROLE OF 1,25-DIHYDROXYVITAMIN D-3-INDUCED METALLOTHIONEIN IN PHOTOPROTECTION AGAINST UVB INJURY IN MOUSE SKIN AND CULTURED RAT KERATINOCYTES

Previously cadmium chloride was successfully used to prevent sunburn cell (SBC) induction in mouse skin in vivo and to promote human cell survival in vitro after UVB exposure, indicating a protective effect of cadmium-induced metallothionein (MT) with the property of antioxidant action. Although cadmium is a potent inducer of MT, the cytotoxic metal is not available for clinical use. The aim of this study is to affirm MT gene expression by the active form of vitamin D-3, 1,25-dihydroxyvitamin D-3, [1,25(OH)(2)D-3] in cultured keratinocytes and examine in vivo and in vitro the photo-protective effects of 1,25(OH)(2)D-3. Northern hybridization with human MT-IIa cDNA showed a significant increase in the gene expression of MT in the cells treated with 1,25(OH)(2)D-3. Intraperitoneal injection and topical application of 1,25(OH)(2)D-3 caused a significant reduction in SBC formation in mouse skin after UVB administration. The experiment showed the existence of an optimum level of 1,25(OH)(2)D-3 for reducing photodamage. The cells exposed to 1,25(OH)(2)D-3 showed increased tolerance (cell survival) to UVB injury. 1,25(OH)(2)D-3-induced MT may act as a radical scavenger in oxygen-mediated UV injury including SBC formation in the skin. These results indicate that 1,25(OH)(2)D-3 may be practically applied to humans for the purpose of photoprotection.