期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms21238943
关键词
HDAC; acetylation; macrophages; inflammation
Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on I kappa B kinase epsilon (IKK epsilon) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKK epsilon although its acetylation was increased. Other pro-inflammatory genes (IL-1 beta, iNOS, TNF alpha) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKK epsilon and iNOS downregulation with potential participation of NF-kappa B transcription factor inhibition. Suppression of HDAC 1-3, activation of NF-kappa B and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches.
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