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J Biol Chem, Vol. 273, Issue 20, 12633-12641, May 15, 1998
From the Program of Developmental Biology, Department of
Comparative Biosciences, University of Wisconsin,
Madison, Wisconsin 53706
Interleukin (IL)-1 is involved in many processes,
including thymic development. However, control of IL-1 expression in
thymic-derived stromal cells (TSC) has not been reported. We found that
IL-1
Transcriptional Regulation of Interleukin-1
Gene by
Interleukin-1 Itself Is Mediated in Part by Oct-1 in Thymic Stromal
Cells
increased steady-state mRNA levels for IL-1
and IL-1
in TSC-936 and TSC-2C4 cells; stability was not a major determinant of
this effect. To study transcriptional regulation of IL-1, we
functionally characterized 4 kilobase pairs of the 5'-flanking region
and first intron of the bovine IL-1 gene. The 
470/+14 fragment was
sufficient to confer maximal responsiveness to IL-1 upon
transfection into these cell lines. Progressive 5' deletions identified
several IL-1-responsive regions, including 308 to 226, which we
further characterized. Electrophoretic mobility shift and supershift
analyses showed that IL-1 induced the ability to form multiple
protein complexes with 261/226 and that one of these contained
nuclear factor Oct-1. A competitor containing a mutated Oct consensus site failed to compete not only for this complex but others as well,
suggesting that this sequence regulates binding of other proteins to
this region. Functional analysis confirmed that this element was
essential for maximal induction of transcription. These findings
document a heretofore undescribed mechanism utilized by TSC for
regulation of IL-1 transcription by IL-1 itself.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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