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(Received for publication, January 24, 1997)
From the Cell Biology and Inflammation Research, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49007
Interleukin-4 (IL-4), an immunoregulatory
cytokine secreted from activated T-helper 2 lymphocytes,
eosinophils, and mast cells, stimulates the expression of a
number of immune system genes via activation of the transcription
factor, STAT6. However, IL-4 can concomitantly suppress the expression
of other immune-related gene products, including
Volume 272, Number 15,
Issue of April 11, 1997
pp. 10212-10219
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
-stimulated
E-selectin Gene Transcription Is Mediated by STAT6 Antagonism of
NF-
B
light chain,
Fc
RI, IL-8, and E-selectin. We demonstrate that IL-4 activates STAT6
in human vascular endothelial cells and that two STAT6 binding sites
are present in the promoter of the E-selectin gene. IL-4-induced STAT6
binding does not activate E-selectin transcription but instead
suppresses tumor necrosis factor 
-induced expression of the
E-selectin gene. STAT6 was found to compete for binding to a region in
the E-selectin gene promoter containing overlapping STAT6 and NF-B
binding sites, effectively acting as an antagonist of NF-B binding
and transcriptional activation. This novel mechanism for IL-4-mediated
inhibition of inflammatory gene expression provides an example of a
STAT factor acting as a transcriptional repressor rather than an
activator.
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