Chung Jin Ho, Seo Jin Young, Lee Mi Kyoung, Eun Hee Chul, Lee Joo Heung, Kang Sewon, Fisher Gary J, Voorhees John J
Department of Dermatology, Seoul National University College of Medicine, and Syungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
J Invest Dermatol. 2002 Aug;119(2):507-12. doi: 10.1046/j.1523-1747.2002.01844.x.
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.
人巨噬细胞金属弹性蛋白酶是基质金属蛋白酶家族的一员，参与弹性蛋白的降解。我们在人体皮肤中对人巨噬细胞金属弹性蛋白酶的紫外线调节进行了体内研究。紫外线照射后16小时内，人体皮肤中的人巨噬细胞金属弹性蛋白酶mRNA达到最大诱导量（11.9倍）。在人体皮肤体内，用抗氧化剂N-乙酰半胱氨酸（20%）和维生素E（5%）预处理可分别平均抑制紫外线对人巨噬细胞金属弹性蛋白酶的诱导达54%和47%。紫外线（每平方厘米30毫焦）和佛波酯（12-O-十四酰佛波醇-13-乙酸酯，50纳摩尔）处理可增加培养的人真皮成纤维细胞中人巨噬细胞金属弹性蛋白酶mRNA和蛋白的表达，但对角质形成细胞无此作用。长期暴露于阳光下的人体皮肤表达大量人巨噬细胞金属弹性蛋白酶蛋白，其与日光性弹力组织变性物质共定位，而在同一个体的防晒皮肤中表达很少。本研究表明，紫外线照射可增加人体皮肤体内人巨噬细胞金属弹性蛋白酶的表达，可能在巨噬细胞和成纤维细胞中增加，且抗氧化剂（N-乙酰半胱氨酸和维生素E）预处理可抑制紫外线诱导的人巨噬细胞金属弹性蛋白酶表达。人巨噬细胞金属弹性蛋白酶与弹力组织变性物质的关联表明，它可能在日光性弹力组织变性的发生中起重要作用，日光性弹力组织变性是人体皮肤体内阳光诱导损伤的标志。
