Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma

Recent studies have demonstrated an effect of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), on airway contractility [via increased airway smooth muscle (ASM) intracellular calcium [Ca2+]i] and remodeling (ASM proliferation and extracellular matrix formation) in the context of airway disease. In the present study, we examined the role of BDNF in allergen-induced airway inflammation using 2 transgenic models: 1) tropomyosin-related kinase B (TrkB) conditional knockin (TrkBKI) mice allowing for inducible, reversible disruption of BDNF receptor kinase activity by administration of 1NMPP1, a PP1 derivative, and 2) smooth muscle–specific BDNF knockout (BDNFfl/fl/SMMHC11Cre/0) mice. Adult mice were intranasally challenged with PBS or mixed allergen (Alternaria alternata, Aspergillus fumigatus, house dust mite, and ovalbumin) for 4 wk. Our data show that administration of 1NMPP1 in TrkBKI mice during the 4-wk allergen challenge blunted airway hyperresponsiveness (AHR) and reduced fibronect...