Ultraviolet modulation of human macrophage metalloelastase in human skin in vivo.

Human macrophage metalloelastase is a member of the matrix metalloproteinase family and is involved in degradation of elastin. We investigated the ultraviolet modulation of human macrophage metalloelastase in human skin in vivo. Ultraviolet induced human macrophage metalloelastase mRNA maximally (11.9-fold) within 16 h post-ultraviolet in human skin. This induction of human macrophage metalloelastase by ultraviolet was inhibited by pretreatment with the antioxidant N-acetyl cystein (20%) and vitamin E (5%) by an average of 54% and 47%, respectively, in human skin in vivo. Ultraviolet (30 mJ per cm2) and phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate, 50 nM) treatment increased expression of human macrophage metalloelastase mRNA and protein in the cultured human dermal fibroblasts, but not in the keratinocytes. Chronically sun-exposed human skin expressed significant amounts of human macrophage metalloelastase protein, which colocalized with the material of solar elastosis, whereas there was little expression in sun-protected skin of the same individuals. This study demonstrates that ultraviolet irradiation increases human macrophage metalloelastase expression in human skin in vivo, possibly in macrophages and fibroblasts, and ultraviolet-induced expression of human macrophage metalloelastase can be inhibited by antioxidant (N-acetyl cystein and vitamin E) pretreatment. Association of human macrophage metalloelastase with elastotic material suggests that it may play an important role in the development of solar elastosis, the hallmark of sun-induced damage in human skin in vivo.