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Retinoic Acid Selectively Inhibits Lipopolysaccharide Induction of
Tissue Factor Gene Expression in Human Monocytes
Paul Oeth,
Jin Yao,
Sao-Tah Fan, and
Nigel Mackman
From the Departments of Immunology and Vascular Biology, The Scripps
Research Institute, La Jolla, CA.
Expression of tissue factor (TF) by activated monocytes in several
diseases leads to disseminated intravascular coagulation. Lipopolysaccharide (LPS)-induced monocyte TF expression is
downregulated by the nuclear hormone all-trans retinoic acid
(ATRA). In this study, we examined the mechanism by which ATRA inhibits
monocyte TF expression. We show that ATRA selectively inhibited LPS
induction of TF expression in human monocytes and monocytic THP-1 cells without affecting LPS induction of tumor necrosis factor- (TNF-) and interleukin-8 (IL-8). Inhibition of TF expression occurred at the
level of transcription as determined by nuclear run-on. ATRA did not
significantly alter the binding or functional activity of the
transcription factors c-Fos/c-Jun and
c-Rel/p65, which are required for LPS induction of the TF
promoter in monocytic cells. In contrast to the ATRA inhibition of the
endogenous TF gene, LPS induction of the cloned TF promoter was not
inhibited by ATRA in transiently transfected THP-1 cells. Our results
demonstrate that ATRA selectively inhibited LPS-induced TF gene
transcription in human monocytic cells by a mechanism that does not
involve repression of AP-1- or
NF- B-mediated transcription.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2857-2865
© 1998 by The American Society of Hematology.
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