EXPRESSION AND FUNCTION OF NERVE GROWTH-FACTOR AND NERVE GROWTH-FACTOR RECEPTOR ON CULTURED KERATINOCYTES

Keratinocytes, a key cellular component both for homeostasis and patho physiologic processes of the skin, secrete a number of cytokines and a re stimulated by several growth factors. Nerve growth factor (NGF) is synthesized in the skin and basal keratinocytes express the low-affini ty nerve growth factor receptor (NGF-R). We present evidence that norm al human keratinocytes in culture express the low- and the high-affini ty NGF-R both at the mRNA level, as determined by reverse-transcriptio n polymerase chain reaction and at the protein level, as shown by cyto fluorimetric analysis. NGF significantly stimulates the proliferation of normal human keratinocytes in culture in a dose-dependent manner. T his effect can be prevented by the addition of both an anti-NGF neutra lizing antibody and a high-affinity NGF-R (trk) specific inhibitor, th e natural alkaloid K252a. By contrast, keratinocyte proliferation is n ot inhibited by an anti - low-affinity NGF-R monoclonal antibody, thus suggesting that NGF effect on human keratinocytes is mediated by the high-affinity NGF-R. Moreover, NGF mRNA is expressed in normal human k eratinocytes and NGF is secreted by keratinocytes in increasing amount s during growth, as detected by enzyme-linked immunosorbent assay. The se results suggest that NGF could act as a cytokine in human skin and take part in disorders of keratinocyte proliferation.