Nerve growth factor and keratinocytes: a role in psoriasis

Nerve growth factor (NGF) is synthesized and released by human keratinocytes. NGF acts as a neurotrophic molecule at the skin level, as it stimulates the sprouting of nerve fibers and regulates the synthesis and expression of neuropeptides. NGF can thus take part in neurogenic inflammation which in turn is involved in the pathogenesis of several inflammatory dermatoses. Human keratinocytes also synthesize and express the low (p75)-and the high-affinity (trk) NGF-receptor (NGF-R). NGF stimulates keratinocyte proliferation which is blocked by the natural alcaloid K252, a specific inhibitor of trk phosphorylation. K252 inhibits keratinocyte proliferation and induces keratinocyte apoptosis, in the absence of exogenous NGF, indicating the existence of an autocrine loop where NGF and trk act as key players. Finally, NGF protein levels are increased in psoriatic as compared to nonlesional and normal skin, and psoriatic keratinocytes express higher amounts of NGF than normal keratinocytes. This review will discuss the above findings in view of a possible involvement of NGF in the pathomechanisms associated with the development of the psoriatic lesion.