Cell-specific involvement of HNF-1ß in a1-antitrypsin gene expression in human respiratory epithelial cells. Hu, Chaobin, and David H. Perlmutter. Departments of Pediatrics and Cell Biology and Physiology, Washington University School of Medicine, and Division of Gastroenterology and Nutrition, St. Louis Children's Hospital, St. Louis, Missouri 63110
APStracts 9:0023L, 2002.
The synergistic action of hepatocyte nuclear factor (HNF)- 1a and HNF-4 plays an important role in expression of the a1-antitrypsin (a1-AT) gene in human hepatic and intestinal epithelial cells. Recent studies have indicated that the a1-AT gene is also expressed in human pulmonary alveolar epithelial cells, a potentially important local site of the lung antiprotease defense. In this study, we examined the possibility that a1-AT gene expression in a human pulmonary epithelial cell line H441 was also directed by the synergistic action of HNF-1a and HNF-4 and/or by the action of HNF-3, which has been shown to play a dominant role in gene expression in H441 cells. The results show that a1-AT gene expression in H441 cells is predominantly driven by HNF-1ß, even though HNF-1ß has no effect on a1-AT gene expression in human hepatic Hep G2 and human intestinal epithelial Caco-2 cell lines. Expression of a1-AT and HNF- 1ß was also demonstrated in primary cultures of human respiratory epithelial cells. HNF-4 has no effect on a1-AT gene expression in H441 cells, even when it is cotransfected with HNF-1ß or HNF-1a. HNF-3 by itself has little effect on a1-AT gene expression in H441, Hep G2, or Caco-2 cells but tends to have an upregulating effect when cotransfected with HNF-1 in Hep G2 and Caco-2 cells. These results indicate the unique involvement of HNF-1ß in a1-AT gene expression in a cell line and primary cultures derived from human respiratory epithelium. 

Received 25 September 2001; accepted in final form 21 October 2001
APS Manuscript Number L271-1.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2002 The American Physiological Society.
Published in APStracts on 14 January 2002