The Primary Mechanism of the IL-10-regulated Antiinflammatory Response is to Selectively Inhibit Transcription

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Jun 7

PMID 15937121

Citations 195

Authors

Peter J Murray

Affiliations

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Abstract

The antiinflammatory cytokine IL-10 inhibits the production of multiple, diverse inflammatory mediators from activated macrophages and dendritic cells, a process requiring STAT3 activation. However, the mechanisms involved in the broad inhibitory effects of IL-10 are controversial. I eliminated the contribution of the major confounding variable to understanding the antiinflammatory response, the 3' UTR region of inflammatory mediator genes, through knock-in mutation and analysis of the effects of IL-10 on transcription rate of inflammatory genes. IL-10 activates STAT3 to act indirectly by selectively inhibiting gene transcription independent of general effects on NF-kappaB or posttranscriptional mRNA processing through a process that reduces the overall transcriptional rate of specific genes.

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