Abstract
We studied the effect of cigarette smoke extract
(CSE) on a three-dimensional (3-D) co-culture
model with epithelial cells and mesenchymal cells
to clarify how epithelial cells protect lung tissue
from cigarette smoke in-vivo.
Two types of gels were prepared. The one was
the co-culture of human fetal lung fibroblasts
(HFL-I) embedded in type-I collagen gel, with alveolar
epithelial cells (A549) cultured covering the top
of the gel. The other was HFL-I cells alone. After
48 hours from CSE exposure, gel contraction, levels
of fibronectin, transforming growth factor
(TGF)--β1 and GSH were assessed.
CSE inhibited fibroblast-mediated gel contraction
and this inhibition was lessened in co-culture
associated with higher GSH concentration and
TGF--β1 level as compared to the level in HFL-I cells
alone. CSE lowered fibronectin level to a lesser
extent in co-culture as compared to the level in
HFL-I cells alone. Exogenous TGF--β1 restored the
inhibition of gel contraction by CSE independent of
GSH level.
Cigarette smoke may interfere with 3-D co-culture
gel contraction by
diminishing GSH, fibronectin and TGF--β1 action
in the epithelial-mesenchymal interaction.