Cell lines and transgenic mice expressing a matrix metalloproteinase-9 promoter-driven reporter gene: Potential for assay of ultraviolet light effects and light-inhibiting compounds

Acute and chronic exposure to ultraviolet (UV) wavelengths in sunlight can cause adverse reactions in exposed areas of the skin and corneas. UV exposure up-regulates the synthesis of Matrix Metalloproteinses (MMPs) and evidence suggests these enzymes mediate tissue damage. Therefore MMP gene activity can serve as a surrogate marker for bioassays. In this study, we tested the possible utility for this purpose of two stably transfected cell lines (from mouse keratinocytes and rabbit epithelial-like corneal cells) and a transgenic mouse line (line 3445), each harboring a DNA construct containing a bacterial beta-galactosidase (LacZ) reporter gene driven by the rabbit MMP-9 transcriptional promoter. We observed only a weak 2-fold maximal induction of LacZ reporter gene expression in the mouse epidermal cell line after exposure to UV-B irradiation (5, 10, 40 mJ/cm(2)) and no significant expression of the reporter gene in the rabbit epithelial-like cell line. Similarly negative results were obtained when primary corneal epithelial cells from human and rabbit were exposed to different doses of UV-B irradiation and endogenous MMP-9 gene expression was assayed by zymography and immunoprecipitation analysis. In contrast, when skin from 3-day-old transgenic mouse line 3445 was exposed to UV-B and UV-A, a clear dose-dependent induction of the LacZ reporter gene occurred and the location of gene expression was dependent on the wave-length of irradiation. These results suggest that line 3445 transgenic mice may serve as a useful tool to quantitatively and qualitatively assess the biological effects of UV light and the efficacy of therapeutic agents.