RESUMEN
The gene expression and regulation of nerve growth factor (NGF) in atopic dermatitis (AD) and the human mast cell line (HMC)-1 was investigated at the molecular level. NGF-stimulation of HMC-1 cells resulted in increases in tryptase activity and histamine contents, paralleled by an increase of tryptase and histamine at the transcriptional level. Also, an increased expression of NGF was found in AD lesions, in association with increased systemic NGF plasma levels. Further cutaneous sources for increased NGF levels were keratinocytes and fibroblasts. These findings demonstrate an increased expression of NGF in AD and effects on tryptase and histamine. Mast cells may be major mediators of neurotrophin effects in AD.
Asunto(s)
Dermatitis Atópica/patología , Regulación de la Expresión Génica/fisiología , Mastocitos/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Células Cultivadas , Dermatitis Atópica/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Histamina/metabolismo , Humanos , Inmunohistoquímica/métodos , Factor de Crecimiento Nervioso/genética , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Serina Endopeptidasas/metabolismo , Piel/citología , Estadísticas no Paramétricas , Factores de Tiempo , TriptasasRESUMEN
BACKGROUND: Neurotrophin 3 (NT-3) is a member of the neurotrophin family, a group of related proteins that are known to regulate neuro-immune interactions in allergic diseases. Their cellular sources and role in the recruitment of mast cell precursors in atopic dermatitis have not been characterized in detail so far. OBJECTIVE: Characterize NT-3 on a transcriptional and translational level in individuals with atopic dermatitis with special focus on mast cells. METHODS: To meet this objective NT-3 levels in the serum of AD patients were measured, the effect of NT-3 on keratinocytes was evaluated and the gene expression and regulation assessed using ELISA, immunohistochemistry and RNA quantification. RESULTS: Systemic levels of NT-3 were found to be higher in individuals with AD as compared to healthy controls. A distinct genetic expression was found in the various cells of the skin. In lesional mast cells of individuals with atopic dermatitis an increased amount of NT-3 was apparent. Functional in vitro experiments demonstrated that NT-3 stimulation led to a suppression of IL-8 secretion by HaCat cells. CONCLUSION: These findings could imply a role for NT-3 in the pathogenesis of allergic skin diseases.