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INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE
Citation:
CHUNG, Y., A. FARRAJ, N. HAYKAL-COATES, S. H. GAVETT, AND M. D. WARD. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 70(12):1020-1026, (2007).
Impact/Purpose:
to investigate whether exposures to PCE could increase the production of neurotrophins in bronchoalveolar lavage fluid (BALF) and sera of PCE challenged mice
Description:
Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmonary challenge with Penicillium chrysogenum extract (PCE) induced dose-dependent allergic asthma-like responses in mice. The aim of this study was to investigate whether exposures to PCE could increase the production of neurotrophins in bronchoalveolar lavage fluid (BALF) and sera of PCE challenged mice. Mice were exposed to 10, 20, 50, or 70 ¿g of PCE by involuntary aspiration four times over one month. BALF was collected before (Day 0), and at Day 1 and 3 following the final exposure. The levels of NGF, NT-3, and NT-4 were determined by ELISA. Lungs collected at Day 0, 1, and 3 were perfusion-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. A single exposure to PCE did not significantly increase the production of the neurotrophins. Exposures to PCE caused an increase in positive immunohistochemical staining for NGF in epithelial and smooth muscle cells in addition to infiltrated cells such as mononuclear cells, eosinophils, and macrophages. When human lung epithelial cells (A549 cell line) were exposed to PCE, neither of neurotrophins was induced. Taken together, mice that received multiple exposures to PCE had dose-dependent increases in NGF, NT-3, and NT-4 in BALF and sera. However, direct exposure to PCE in lung epithelial cells did not cause the induction of neurotrophins. This is the first study to link fungal allergic asthma in an experimental model with enhanced production of neurotrophins in the airways.