Skin photoaging is a
complex, multifactorial process resulting in functional and structural changes
of the skin, and different phenotypes from chronological skin aging are
well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a
skin photoaging animal model. However, differences in morphology and gene
expression patterns between UV-induced and chronological skin changes in this mouse
model have not been fully elucidated. Here we investigated differences in
histopathology and cytokine expression between UV-irradiated and non-irradiated
aged hairless mice to clarify the factor(s) that differentiate photoaging from
chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were
divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control
mice) groups. Irradiation was performed three times per week for 10 weeks. In
addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age
without UV irradiation (aged mice). Histopathologies revealed that the
flattening of dermal-epidermal junctions and epidermal thickening were observed
only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the
epidermis, the thickening of elastic fibers in the reticular dermis, and the
accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as
compared to non-irradiated aged mice. Quantitative PCR analyses revealed that
UV-irradiated mice showed an increase in the expression of IFN-γ. In
contrast, aged mice exhibited proportional up-regulation of both
pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio,
an indicator for the balance of pro-inflammatory and anti-inflammatory
cytokines, was significantly higher in UV-irradiated mice as compared to
control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was
also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a
spontaneous skin photoaging model we recently reported. Thus, an imbalance
between pro-inflammatory and anti-inflammatory cytokines might be
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