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1 Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; and 2 Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan 482021
Surfactant protein B (SP-B) is a
developmentally and hormonally regulated lung protein that is required
for normal surfactant function. We generated transgenic mice carrying
the human SP-B promoter (
1,039/+431 bp) linked to chloramphenicol
acetyltransferase (CAT). CAT activity was high in lung and
immunoreactive protein localized to alveolar type II and bronchiolar
epithelial cells. In addition, thyroid, trachea, and intestine
demonstrated CAT activity, and each of these tissues also expressed low
levels of SP-B mRNA. Developmental expression of CAT activity and SP-B mRNA in fetal lung were similar and both increased during explant culture. SP-B mRNA but not CAT activity decreased during culture of
adult lung, and both were reduced by transforming growth factor (TGF)-
1. Treatment of adult mice with intratracheal
bleomycin caused similar time-dependent decreases in lung SP-B mRNA and CAT activity. These findings indicate that the human SP-B promoter fragment directs tissue- and lung cell-specific transgene expression and contains cis-acting elements involved in regulated
expression during development, fetal lung explant culture, and
responsiveness to TGF- and bleomycin-induced lung injury.
transforming growth factor-; lung explant culture; bleomycin
lung injury; dexamethasone; lung development
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