Review Article
Keiichi Hiramoto, Hiromi Ko
Abstract
Irradiation with long-term ultraviolet (UV) A induces photoaging. The mechanisms responsible for the skin structural changes induced by long-term UVA irradiation remain unknown. In this study, we targeted gp91phox and conducted analysis of the mechanism of the photoaging induced by UVA. Male C57BL/6j and gp91phox-knockout (gp91phox-/-) mice were used in this study. The dorsal skin was locally exposed to UVA after covering the remaining body surface with aluminum foil at a dose of 110 kJ/m2 using a FL20SBLB-A lamp for three times a week for 20 weeks. We unexpectedly found that the hypertrophy of a skin and the inovasion of the inflammatory cells were not induced in the UVA long-term radiation gp91phox-/- mice. The levels of plasma nitrogen oxide (NO2/NO3), tumor necrosis factor-α (TNF-α) and interleyukin-1 (IL-1) all increased following UVA irradiation in the C57BL/6j mice; however, there were no changes in the gp91phox-/- mice. Decreases in the expressions of collagen I and increases in the expression of metalloproteinase-1 (MMP-1) were observed following UVA irradiation in the C57BL/6j mice, whereas decreased expressions were not observed in the UVA-irradiated gp91phox-/- mice. In addition, the expression of the gp91phox on the surface of neutrophils was increased by UVA irradiation. Furthermore, the neutrophils-depleted mice exhibited strongly inhibited UVA-induced photoaging. These results clearly indicate that NADPH oxidase is activated by gp91phox, which is expressed on the surface in response to the increased expression of neutrophils induced by UVA irradiation, which subsequently simulates the generation of reactive oxygen species (ROS). This system may play an important role in photoaging; however, further studies are needed to confirm these findings.