Author(s)

Masaaki Sakura, Yoichi Chiba, Emi Kamiya, Ayako Furukawa, Noriko Kawamura, Masanao Niwa, Minoru Takeuchi, Yasushi Enokido, Masanori Hosokawa

Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
Faculty of Life Science, Kyoto Sangyo University, Kyoto, Japan.
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan.
Fundamental Research Laboratory, General Research & Development Institute, Hoyu Co., Ltd., Nagakute, Japan.

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 a key factor to differentiate photoaged skin from chronologically-aged skin.

Photoaged Skin, Chronologically-Aged Skin, Pro-Inflammatory Cytokines, Anti-Inflammatory Cytokines, Hairless Mice

Sakura, M. , Chiba, Y. , Kamiya, E. , Furukawa, A. , Kawamura, N. , Niwa, M. , Takeuchi, M. , Enokido, Y. and Hosokawa, M. (2014) Differences in the Histopathology and Cytokine Expression Pattern between Chronological Aging and Photoaging of Hairless Mice Skin. Modern Research in Inflammation, 3, 82-89. doi: 10.4236/mri.2014.33010.