Rationale
Epithelial remodelling in asthma is characterised by goblet cell hyperplasia and mucus hypersecretion
for which no therapies exist. Differentiated bronchial air-liquid interface cultures
from asthmatic children display high goblet cell numbers. Epidermal growth factor and
its receptor have been implicated in goblet cell hyperplasia.
Objectives
We hypothesised that EGF removal or tyrphostin AG1478 treatment of differentiating air-liquid
interface cultures from asthmatic children would result in a reduction of epithelial goblet
cells and mucus secretion.
Methods
In Aim 1 primary bronchial epithelial cells from non-asthmatic (n = 5) and asthmatic (n = 5)
children were differentiated under EGF-positive (10ng/ml EGF) and EGF-negative culture
conditions for 28 days. In Aim 2, cultures from a further group of asthmatic children (n = 5)
were grown under tyrphostin AG1478, a tyrosine kinase inhibitor, conditions. All cultures
were analysed for epithelial resistance, markers of differentiation using immunocytochemistry,
ELISA for MUC5AC mucin secretion and qPCR for MUC5AC mRNA.
Results
In cultures from asthmatic children the goblet cell number was reduced in the EGF negative
group (p = 0.01). Tyrphostin AG1478 treatment of cultures from asthmatic children had