PMID: 9192770Jun 15, 1997Paper

Interleukin-10 inhibits interferon-gamma-induced intercellular adhesion molecule-1 gene transcription in human monocytes.

Blood
S SongA Finnegan

Abstract

Interleukin-10 (IL-10) is a potent monocyte regulatory cytokine that inhibits gene expression of proinflammatory mediators. In this study, we investigated the mechanism by which IL-10 downregulates expression of intercellular adhesion molecule-1 (ICAM-1) on the cell surface of normal human monocytes activated with interferon-gamma (IFN-gamma). IL-10 inhibition of IFN-gamma-induced ICAM-1 expression was apparent as early as 3 hours and was blocked by an anti-IL-10 antibody but not by an isotype-matched control antibody. Northern blot analysis showed that IL-10 reduced the accumulation of ICAM-1 mRNA in IFN-gamma-stimulated monocytes. IL-10 inhibition of ICAM-1 steady-state mRNA was detected at 3 hours and remained at 24 hours. Nuclear run-on transcription assays showed that IL-10 inhibited the rate of IFN-gamma-induced transcription of the ICAM-1 gene, and mRNA stability studies showed that IL-10 did not alter the half-life of IFN-gamma-induced ICAM-1 message. Thus, IL-10 inhibits IFN-gamma-induced ICAM-1 expression in monocytes primarily at the level of gene transcription. Activation of IFN-gamma-responsive genes requires tyrosine phosphorylation of the transcriptional factor STAT-1alpha (signal transducer and activator of tran...Continue Reading

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