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Vol. 291, Issue 1, 367-373, October 1999
Gene
Expression at the Transcriptional Level in Bleomycin Hamster Model of
Lung Fibrosis1
Department of Molecular Biosciences, School of Veterinary Medicine,
University of California, Davis, California
This study was undertaken to investigate whether treatment with the
antifibrotic drug pirfenidone (PD) down-regulates the bleomycin
(BL)-induced overexpression of transforming growth factor (TGF)-
gene in the lungs. Hamsters were intratracheally
instilled with SA or BL (6.5 U/kg/4 ml) under anesthesia. They were fed a diet containing 0.5% PD or the same control diet (CD) without the
drug 2 days before and throughout the study. After the animals were
sacrificed, their lungs were appropriately processed. The BL treatment
elevated the total influx of inflammatory cells, including macrophages,
by severalfold at different days in bronchoalveolar lavage fluid (BALF)
from hamsters in BL + CD groups, relative to the corresponding SA + CD
control groups. Treatment with PD significantly (P 
.05) suppressed the influx of inflammatory cells and macrophages at
day 7 in the BL + PD groups, relative to the corresponding BL + CD
groups. In addition, the levels of TGF- in BALF from hamsters in BL + CD groups were elevated by 2.6- to 4.5-fold at different days,
relative to the corresponding SA + CD groups. Treatment with PD
significantly (P .05) reduced the TGF-
protein in BALF from BL + PD groups at 14 and 21 days, when compared
with the corresponding BL + CD groups. The intratracheal instillation
of BL significantly (P .05) elevated the TGF- mRNA at 7, 14, and 21 days in BL + CD groups, relative to the corresponding SA + CD groups, and treatment with PD significantly (P .05) suppressed the TGF- gene expression
in BL + PD groups at these times, when compared with the corresponding
BL + CD groups. Nuclear runoff studies revealed that PD suppressed the
BL-induced increase in TGF- gene transcription by 33%. It was
concluded that one of the mechanisms for antifibrotic effect of PD is
its ability to suppress the BL-induced overexpression of TGF- gene at the transcriptional level.
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