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(Received for publication, March 8, 1996, and in revised form, April 23, 1996)
From the Hanson Centre for Cancer Research, Institute of Medical
and Veterinary Science,
Adelaide, South Australia 5000, Australia
Adenosine-uridine (AU) instability elements,
found in the 3
Volume 271, Number 33,
Issue of August 16, 1996
pp. 20108-20112
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
-untranslated regions of numerous mRNAs, target
these mRNAs for rapid degradation. In addition, the degradation
rate of some mRNAs that contain AU instability elements can change.
This modulation of mRNA stability is an important component in the
regulation of expression of many of the cytokines that control the
production and function of blood cells. However, it has not been clear
whether the stabilities of individual cytokine mRNAs that contain
AU instability elements are coordinately regulated or whether different
mRNAs can be independently regulated. We have investigated the
influence of the cytokine synthesis inhibitory factor interleukin
(IL)-10 on the turnover of granulocyte-colony stimulating factor
(G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and
IL-10 mRNAs in human blood monocytes stimulated with
lipopolysaccharide. We find that all three mRNAs are destabilized
in response to IL-10 but at different times. The G-CSF and GM-CSF
mRNAs respond similarly, being rapidly destabilized, consistent
with a direct influence of IL-10 receptor-mediated signals on the
stability of these mRNAs. In contrast the IL-10 mRNA became
unstable only after several hours of treatment with IL-10, suggesting
that the IL-10 mRNA, although it also contains AU instability
elements, is not co-regulated with the G-CSF and GM-CSF mRNAs but
is regulated by a secondary factor produced in response to IL-10.
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