R&D Department of Dermatological Sciences, POLA Chemical Industries, Inc., Yokohama, Japan.
J Dermatol Sci. 2010 Dec;60(3):151-8. doi: 10.1016/j.jdermsci.2010.09.001. Epub 2010 Sep 24.
Repeated exposure to ultraviolet (UV) rays damages skin connective tissue, which is thought to be associated with wrinkle formation. We hypothesized that repeated mild inflammation may cause the connective tissue alterations in photoaging.
To clarify the behavior of neutrophils and neutrophil elastase (NE) activity in the photoaging process and to examine the mechanisms of connective tissue damage resulting from NE in photoaging.
Mouse dorsal skin was irradiated with a suberythemal dose of UVB three times a week. After 5 or 10 weeks of irradiation, neutrophils were investigated by light microscopy and transmission electron microscopy. NE activity was examined by in situ zymography. Activation of proMMP-2 and proMMP-1 by NE both in the purified enzyme and in human skin fibroblast culture was examined by gelatin zymography or immunoblotting respectively.
Both neutrophil infiltration and NE activity were elevated in photoaging. Furthermore, activated MMP-2 and MMP-1 were increased by NE treatment in a dose-dependent manner.
In the present study, we demonstrated that neutrophil infiltration and NE activity are elevated in the chronic UVB-irradiated skin of hairless mice and we confirmed the involvement of NE in MMP activation. These data suggest that NE indirectly plays a role in skin photoaging through MMP activation.
反复暴露于紫外线 (UV) 射线会损伤皮肤结缔组织，这被认为与皱纹形成有关。我们假设反复轻度炎症可能导致光老化过程中的结缔组织改变。
阐明中性粒细胞和中性粒细胞弹性蛋白酶 (NE) 在光老化过程中的行为，并研究 NE 在光老化中导致结缔组织损伤的机制。
每周三次用亚红斑剂量的 UVB 照射小鼠背部皮肤。照射 5 或 10 周后，通过光镜和透射电镜观察中性粒细胞。通过原位酶谱法检查 NE 活性。通过明胶酶谱或免疫印迹分别在纯化酶和人皮肤成纤维细胞培养物中检查 NE 对 proMMP-2 和 proMMP-1 的激活作用。
光老化时中性粒细胞浸润和 NE 活性均升高。此外，NE 处理以剂量依赖性方式增加激活的 MMP-2 和 MMP-1。
在本研究中，我们证明了无毛小鼠慢性 UVB 照射皮肤中中性粒细胞浸润和 NE 活性升高，并证实了 NE 在 MMP 激活中的作用。这些数据表明，NE 通过 MMP 激活间接参与皮肤光老化。
