Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects

Abstract

Recently, the pivotal role of brain-derived neurotrophic factor (BDNF) has been described in allergic asthma. However, the role of this neurotrophin in atopic dermatitis (AD) still remains unknown. The aim of this study was to investigate the functional role of BDNF on eosinophils and to assess BDNF levels in patients with AD and nonatopic control subjects. Methods p75 Neurotrophin receptor and tyrosine kinase B receptor expression was demonstrated by using FACS analysis and immunohistochemistry. BDNF levels were assessed with ELISA and FACS analysis. Chemotactic activity (modified Boyden chamber assay), eosinophil cationic protein release (fluoroenzyme immunoassay), respiratory burst (lucigenin-dependent chemiluminescence), and apoptosis (Nicoletti protocol and Annexin-V method) assays were used to assess BDNF functional activity. BDNF levels were increased in serum, plasma, eosinophils, and supernatants of stimulated eosinophils from patients with AD compared with levels seen in nonatopic control subjects ( P < .05-.001). In addition, p75 neurotrophin receptor and tyrosine kinase B expression was higher on eosinophils from patients with AD compared with that seen on eosinophils from nonatopic control subjects ( P < .05-.001). Eosinophil apoptosis was inhibited by BDNF ( P < .05-.01) and chemotactic index was increased ( P < .001) in BDNF-stimulated eosinophils from patients with AD, whereas this effect was not shown in eosinophils from nonatopic control subjects. However, no response of BDNF through the release of eosinophil cationic protein or reactive oxygen species was found. This study provides the first evidence for a functional role of BDNF on eosinophils from patients with AD, probably mediated by an increased expression of BDNF receptors compared with that seen in nonatopic control subjects. In addition, higher intracellular, serum, and plasma BDNF levels, as well as the release of BDNF by eosinophils, underline the particular importance of BDNF in patients with AD, pointing to new pathophysiologic aspects of this chronic inflammatory skin disease.