title: Neuroendocrine cells of nasal mucosa are a cellular source of brain-derived neurotrophic factor.
abstract: There is growing evidence for extensive interaction between sensory neurons, immune and mucosal epithelial cells during airway inflammation and hyperreactivity. This neuro-immune cross-talk (neurogenic inflammation) involves different groups of mediators, which include the neurotrophin family (nerve growth factor, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and -4). Neurotrophins modulate airway inflammation by enhancing sensory nerve excitability and production of neuropeptides, and by interaction with different immune cell types. In the present study, it was questioned whether airway epithelial cells express BDNF, and if proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma) and a glucocorticoid (budesonide) affect this expression. Primary cultures of nasal epithelial cells were used. It was found that BDNF was stored in chromogranin A-containing secretory granules of specialised epithelial cells, i.e. neuroendocrine cells, and was secreted in a polarised manner. Apical secretion appears to be constitutive, whereas basolateral secretion is markedly enhanced upon stimulation with cytokines. This enhanced basolateral secretion was not due to enhanced synthesis and was not affected by inhibitors of the processing enzymes, such as furin and the metalloproteinases involved in the maturation of BDNF, but was considerably diminished by budesonide. Therefore, airway mucosa might contribute to neurogenic inflammation through increased secretion of brain-derived neurotrophic factor by neuroendocrine cells under inflammatory conditions.
authors.affiliation: Division of Pulmonary Medicine, Dept of Internal Medicine, Geneva University Hospitals, Geneva, Switzerland. Lan.H.Jornot@hcuge.ch
authors.forename: L
authors.initials: L
authors.lastname: Jornot
authors.forename: J S
authors.initials: JS
authors.lastname: Lacroix
authors.forename: T
authors.initials: T
authors.lastname: Rochat