Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon.

Abstract:

: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 gamma (IFNgamma)- or IFNbeta-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/beta-mediated antiviral activity. Finally, the IL-10-mediated suppression of LPS-stimulated IP-10 production could be rescued by cotreatment with IFNbeta.

journal_name

Blood

journal_title

Blood

authors

Tebo JM,Kim HS,Gao J,Armstrong DA,Hamilton TA

subject

Has Abstract

pub_date

1998-12-15 00:00:00

pages

4742-9

issue

12

eissn

0006-4971

issn

1528-0020

journal_volume

92

pub_type

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