Production and function of pigment epithelium-derived factor in isolated skin keratinocytes.

Pigment epithelium-derived factor (PEDF) is a multifunctional factor with potent anti-angiogenic activity that may play a role in skin homoeostasis and wound healing. Analysis of PEDF levels demonstrated that PEDF levels are high in normal skin but quite low in early wounds. As previous studies have suggested that keratinocytes can produce PEDF, we investigated how conditions that mimic those found at sites of injury influence PEDF production by keratinocytes in vitro. Both injury by mechanical disruption (scratch assay) and treatment of human keratinocytes with inflammatory cytokines (IL-1β, IL-6 and TNF-α) inhibited PEDF expression. We next examined how PEDF affects keratinocyte functions that are important in tissue repair. Treatment of keratinocytes with exogenous PEDF enhanced keratinocyte adhesion, therefore impairing migration, while having no effect on cell proliferation. The results suggest that modulation of PEDF levels may play a pivotal role in skin homoeostasis and the response of keratinocytes to injury or inflammatory insults.