Neutrophil elastase contributes to extracellular matrix damage induced by chronic low-dose UV irradiation in a hairless mouse photoaging model

Abstract

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.