Increased neurotrophin production in a Penicillium chrysogenum-induced allergic asthma model in mice

Abstract

Neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-3, have been implicated in the pathogenesis of many features and symptoms of asthma. The role of neurotrophins in fungal allergic asthma, however, is unknown. Repeated pulmonary challenge with Penicillium chrysogenum extract (PCE) induces dose-dependent allergic asthma-like responses in mice. The aim of this study was to investigate whether neurotrophins are involved in the PCE-induced allergic airway response in mice. Mice were exposed to 10, 20, 50, or 70 microg PCE by involuntary aspiration 4 times over 1 mo. Bronchial alveolar lavage fluid (BALF) was collected immediately before and after the final exposure. The levels of NGF, NT-3, and NT-4 were determined by enzyme-linked immunosorbent assay (ELISA). The lungs were fixed and processed for immunohistochemical examination of NGF production. PCE-exposed mice had dose-dependent increases in NGF, NT-3, and NT-4 in both BALF and sera. Exposures to PCE produced elevation in positive immunohistochemical staining for NGF in the airway epithelium and smooth muscle cells, in addition to infiltrated cells such as mononuclear cells, eosinophils, and macrophages. Taken together, this is the first study to link fungal allergic asthma in an experimental model with enhanced production of neurotrophins in the airways, and suggests that neurotrophins may play a role in the etiology of mold-induced asthma in humans.