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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4742-4749
Interleukin-10 Suppresses IP-10 Gene Transcription by Inhibiting
the Production of Class I Interferon
Julie M. Tebo,
Hee Sun Kim,
Jing Gao,
David A. Armstrong, and
Thomas A. Hamilton
From the Department of Immunology, Lerner Research Institute,
Cleveland Clinic Foundation, Cleveland, OH.
Interleukin-10 (IL-10) selectively inhibited lipopolysaccharide
(LPS)-induced chemoattractant cytokine gene expression: levels of IP-10
mRNA were markedly suppressed in IL-10-treated mouse peritoneal
macrophages, whereas the expression of the RANTES mRNA was only
modestly reduced. IL-10 inhibited IP-10 mRNA accumulation by reducing
IP-10 gene transcription as demonstrated by nuclear run-on analysis.
Interestingly, the ability of IL-10 to inhibit expression of IP-10 was
dependent on the inducing stimulus; IL-10 did not suppress interferon
 (IFN)- or IFN -stimulated IP-10 transcription or mRNA
accumulation. These results suggested that IL-10 might act indirectly
to suppress IP-10 expression by inhibiting LPS-induced class I IFN
production. This hypothesis was supported by the following
observations. First, LPS-induced IP-10 mRNA expression was blocked in
cells cotreated with cycloheximide. Second, IL-10 inhibited the
production of IFN /-mediated antiviral activity. Finally, the
IL-10-mediated suppression of LPS-stimulated IP-10 production could be
rescued by cotreatment with IFN.
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