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

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)-1alpha 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-1alpha secretion by keratinocytes was significantly increased in the fifth cultures compared with the second cultures (P<0.005). CONCLUSIONS These findings suggest that IL-1alpha secretion increases as cells grow older, and the increased secretion of IL-1alpha 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-1alpha 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-1alpha by aged keratinocytes in the aged skin may play a role in the accentuated cutaneous pigmentation and other skin ageing.