TY - JOUR
T1 - Cell-specific involvement of HNF-1β in α1-antitrypsin gene expression in human respiratory epithelial cells
AU - Hu, Chaobin
AU - Perlmutter, David H.
PY - 2002
Y1 - 2002
N2 - The synergistic action of hepatocyte nuclear factor (HNF)-1α and HNF-4 plays an important role in expression of the α1-antitrypsin (α1-AT) gene in human hepatic and intestinal epithelial cells. Recent studies have indicated that the α1-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 α1-AT gene expression in a human pulmonary epithelial cell line H441 was also directed by the synergistic action of HNF-1α 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 α1-AT gene expression in H441 cells is predominantly driven by HNF-1β, even though HNF-1β has no effect on α1-AT gene expression in human hepatic Hep G2 and human intestinal epithelial Caco-2 cell lines. Expression of α1-AT and HNF-1β was also demonstrated in primary cultures of human respiratory epithelial cells. HNF-4 has no effect on α1-AT gene expression in H441 cells, even when it is cotransfected with HNF-1β or HNF-1α. HNF-3 by itself has little effect on α1-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-1β in α1-AT gene expression in a cell line and primary cultures derived from human respiratory epithelium.
AB - The synergistic action of hepatocyte nuclear factor (HNF)-1α and HNF-4 plays an important role in expression of the α1-antitrypsin (α1-AT) gene in human hepatic and intestinal epithelial cells. Recent studies have indicated that the α1-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 α1-AT gene expression in a human pulmonary epithelial cell line H441 was also directed by the synergistic action of HNF-1α 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 α1-AT gene expression in H441 cells is predominantly driven by HNF-1β, even though HNF-1β has no effect on α1-AT gene expression in human hepatic Hep G2 and human intestinal epithelial Caco-2 cell lines. Expression of α1-AT and HNF-1β was also demonstrated in primary cultures of human respiratory epithelial cells. HNF-4 has no effect on α1-AT gene expression in H441 cells, even when it is cotransfected with HNF-1β or HNF-1α. HNF-3 by itself has little effect on α1-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-1β in α1-AT gene expression in a cell line and primary cultures derived from human respiratory epithelium.
KW - Pneumocytes
KW - Protease inhibitors
KW - Tissue-specific gene expression
UR - http://www.scopus.com/inward/record.url?scp=0036088988&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00271.2001
DO - 10.1152/ajplung.00271.2001
M3 - Article
C2 - 11880302
AN - SCOPUS:0036088988
SN - 1040-0605
VL - 282
SP - L757-L765
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 4 26-4
ER -