The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription

作者：Peter J. Murray · 发表于：Proceedings of the National Academy of Sciences · 年份：2005 · DOI：10.1073/pnas.0500419102 · 被引用次数：402 · 研究领域：Cytokine Signaling Pathways and Interactions、Immune Response and Inflammation、NF-κB Signaling Pathways

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.