Interactions between the nerve system and the skin are thought to be important for inflammatory skin diseases, e.g. atopic dermatitis (AD). Little is currently known about the capacity of skin cells to synthesize mediators which sustain and/or enhance neural functions in the skin. From previous studies it has been concluded that human dermal fibroblasts (FB), but not epidermal keratinocytes (KC) may support growth of melanocytes by virtue of their capacity to express neurotrophic factor (NT)-3. The present study assessed whether KC, although not being able to express NT-3, may express brain derived nerve growth factor (BDNF) and the recently described neurotrophin NT-4. As demonstrated by RT-PCR analysis followed by endonuclease digestion, normal human KC as well as primary human FB constitutively expressed high amounts of BDNF mRNA. In contrast, only KC, but not FB, expressed mRNA for NT-4, while NT-3 specific transcripts were not detectable in KC. In KC, NT-4 and BDNF expression was enhanced in a time dependent manner by exposure of cells to phorbol-ester, ultraviolet B radiation, and, in particular, interferon-γ (IFN-γ). IFN-γ induced NT-4 expression may be of in-vivo relevance, because in atopy-patch-test lesions of AD patients, increased in-situ expression of IFN-γ mRNA was associated with increased NT-4 mRNA expression. These studies for the first time demonstrate that KC express neurotrophins, in particular BDNF and NT-4, and thus may affect melanocyte or nerve cell growth. The observation that NT-4 and NT-3 expression in KC versus FB is mutually exclusive suggests a highly differentiated role for both cell types in modulating nerve cell or melanocyte growth under inflammatory conditions.