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Correlation between age and the secretions of melanocyte-stimulating cytokines in cultured keratinocytes and fibroblasts

Authors

  • M. Okazaki,

    1. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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  • K. Yoshimura,

    1. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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  • G. Uchida,

    1. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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  • K. Harii

    1. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Mutsumi Okazaki
Email: okazaki-m@umin.ac.jp

Summary

Background  The majority of skin changes associated with ageing are caused by photoageing and reflect cumulative sun exposure. Although the actinic damage plays a major role in skin pigmentation, it is also important to examine the effects of chronological cellular ageing on the pigmentation. The chief cellular components of the skin other than melanocytes are keratinocytes and fibroblasts, and the influences of age-related changes in those cells on skin pigmentation have not been elucidated.

Objective  To clarify the effects of cellular ageing of keratinocytes and fibroblasts on age-related skin pigmentation.

Methods  Using ELISA analysis, we measured the level of melanogenic cytokines secreted by cultured keratinocytes and fibroblasts derived from skin of various chronological ages. We also compared the cytokine secretion by cultured keratinocytes between the second and fifth cultures.

Results  There was no correlation between age and hepatocyte growth factor (HGF), stem cell factor (SCF), and basic fibroblast growth factor (bFGF) secretion by fibroblasts. On the other hand, a significant positive correlation existed between age and interleukin ((IL)-1α secretion (R2 = 0·50, P = 0·002), and a relatively weak correlation existed between age and endothelin-1 (ET-1) secretion (R2 = 0·17, P = 0·051, not significant). The IL-1α secretion by keratinocytes was significantly increased in the fifth cultures compared with the second cultures (P < 0·005).

Conclusions  These findings suggest that IL-1α secretion increases as cells grow older, and the increased secretion of IL-1α by aged keratinocytes may stimulate HGF production in dermal fibroblasts paracrinely and ET-1 production in keratinocytes autocrinely, which stimulates melanocyte proliferation and induces an increase of tyrosinase activity in melanocytes. Because IL-1α is a primary mediator that responds to inflammation and injury, the transcription of genes involved in skin inflammation may be persistently induced in the aged skin. Thus the increased secretion of IL-1α by aged keratinocytes in the aged skin may play a role in the accentuated cutaneous pigmentation and other skin ageing.

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