Neurotrophin-4 production by human epidermal keratinocytes: Increased expression in atopic dermatitis

Chronic inflammatory conditions of human skin, such as prurigo lesions of a topic dermatitis, are characterized clinically by intense pruritus and hist ologically by increased innervation. Regulation of skin innervation is thou ght to depend on neurotrophic factors. In this study, human skin cells were identified as a source of neurotrophins. Cultured keratinocytes expressed neurotrophin-4, whereas dermal fibroblasts expressed neurotrophin-3. In vit ro stimulation with interferon-gamma, a marker cytokine for atopic eczema, induced keratinocyte neurotrophin-4 production, which was able to support g rowth of a neuroglioblastoma-derived cell line. In vivo, immunohistochemist ry of human skin for neurotrophins showed neurotrophin-4 staining in the ep idermal layer and neurotrophin-3 staining in the dermal compartment. Neurot rophin-4 but not neurotrophin-3 expression was markedly increased in interf eron-gamma-injected skin. Prurigo lesions of atopic dermatitis skin were ch aracterized by intense epidermal staining for neurotrophin-4, suggesting a pathophysiologic role for this neurotrophin in the increased innervation ch aracteristic for these skin lesions. This study demonstrates differential e xpression and regulation of neurotrophins in human skin. It also identifies keratinocyte-derived neurotrophin-4 as a possible link between the immune and the nerve system of human skin.