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Volume 271, Number 43,
Issue of October 25, 1996
pp. 26783-26793
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Retinoic Acid-induced Transcriptional Modulation of the Human
Interferon- Promoter
(Received for publication, July 29, 1996)
Marco
Cippitelli
,
Jianping
Ye
§
,
Vincenzo
Viggiano
§
,
Antonio
Sica
§
,
Paritosh
Ghosh
§
,
Alberto
Gulino
¶
,
Angela
Santoni
''
and
Howard A.
Young
§
From the Intramural Research Support Program,
Scientific Application International Corporation Frederick, and the
§ Laboratory of Experimental Immunology, Division of Basic
Science, National Cancer Institute-Frederick Cancer Research and
Development Center, Frederick, Maryland 21702-1201, the
¶ Department of Experimental Medicine, University of L'Aquila,
67100 L'Aquila, Italy, the Department of Experimental Medicine
and Pathology, University ``La Sapienza,'' Roma 00158, Italy, and the
'' Laboratory of Pathophysiology, Regina Elena Cancer Institute, Roma
00158, Italy
Disregulation of vitamin A metabolism is able to
generate different immunological effects, including altered response to
infection, reduced IgG production, and differential regulation of
cytokine gene expression (including interleukin-2 and -4 and
interferon- (IFN- )). In particular, IFN- gene expression is
significantly affected by vitamin A and/or its derivatives
(e.g. retinoic acid (RA)). Here, we analyze the effect of
retinoic acid on IFN- transcription. Transient transfection assays
in the human T lymphoblastoid cell line Jurkat demonstrated that the
activation of the IFN- promoter was significantly down-regulated in
the presence of RA. Surprisingly, two different AP-1/CREB-ATF-binding
elements situated in the initial 108 base pairs of the IFN- promoter
and previously shown to be critical for transcriptional activity were
unaffected by RA. Utilizing promoter deletions and electrophoretic
mobility shift analysis, we identified a USF/EGR-1-binding element
cooperating in the modulation of IFN- promoter activity by RA. This
element was found to be situated in a position of the IFN- promoter
close to a silencer element previously identified in our laboratory.
These results suggest that direct modulation of IFN- promoter
activity is one of the possible mechanisms involved in the inhibitory
effect of retinoids on IFN- gene expression.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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