TGF-beta and glutathione promote tissue repair in cigarette smoke induced injury.
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)-beta 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-beta1 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-beta1 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-beta1 action in the epithelial-mesenchymal interaction.
Department of Integrated Pulmonology, Tokyo Medical and Dental University, Tokyo, Japan.
Chika
C
Noguchi
Takeshi
T
Umino
Yasunari
Y
Miyazaki
Torahiko
T
Jinta
Yutaka
Y
Usui
Yasuyuki
Y
Yoshizawa
D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D005353:Fibronectins; D011994:Recombinant Proteins; D012906:Smoke; D016212:Transforming Growth Factor beta; D005978:Glutathione