期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 207, 期 10, 页码 2081-2088出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100414
关键词
-
资金
- Arthritis Research Campaign
- Kennedy Institute Trustees
- Medical Research Council
- MRC [G0700128] Funding Source: UKRI
- Medical Research Council [G0700128] Funding Source: researchfish
IL-10 plays a central nonredundant role in limiting inflammation in vivo. However, the mechanisms involved remain to be resolved. Using primary human macrophages, we found that IL-10 inhibits selected inflammatory genes, primarily at a level of transcription. At the TNF gene, this occurs not through an inhibition of RNA polymerase II (Pol II) recruitment and transcription initiation but through a mechanism targeting the stimulation of transcription elongation by cyclin-dependent kinase (CDK) 9. We demonstrated an unanticipated requirement for a region downstream of the TNF 3' untranslated region (UTR) that contains the nuclear factor kappa B (NF-kappa B) binding motif (kappa B4) both for induction of transcription by lipopolysaccharide (LPS) and its inhibition by IL-10. IL-10 not only inhibits the recruitment of RelA to regions containing kappa B sites at the TNF gene but also to those found at other LPS-induced genes. We show that although IL-10 elicits a general block in RelA recruitment to its genomic targets, the gene-specific nature of IL-10's actions are defined through the differential recruitment of CDK9 and the control of transcription elongation. At TNF, but not NFKBIA, the consequence of RelA recruitment inhibition is a loss of CDK9 recruitment, preventing the stimulation of transcription elongation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据