期刊
JOURNAL OF INNATE IMMUNITY
卷 8, 期 2, 页码 143-155出版社
KARGER
DOI: 10.1159/000442254
关键词
Innate immune response; DNA-damage response; Ataxia telangiectasia mutated; Interferon; 8-Oxoguanine
类别
资金
- National Institutes of Health grant [NCATS UL1TR001439]
- NHLBI [HHSN-268201000037C]
- NIAID [AI062885]
- IHII mini-center pilot
- NIEHS [P30 ES006676]
- [DMS-1361411/DMS-1361318]
The airway mucosa is responsible for mounting a robust innate immune response (IIR) upon encountering pathogen-associated molecular patterns. The IIR produces protective gene networks that stimulate neighboring epithelia and components of the immune system to trigger adaptive immunity. Little is currently known about how cellular reactive oxygen species (ROS) signaling is produced and cooperates in the IIR. We discuss recent discoveries about 2 nuclear ROS signaling pathways controlling innate immunity. Nuclear ROS oxidize guanine bases to produce mutagenic 8-oxoguanine, a lesion excised by 8-oxoguanine DNA glycosylase1/AP-lyase (OGG1). OGG1 forms a complex with the excised base, inducing its nuclear export. The cytoplasmic OGG1:8-oxoG complex functions as a guanine nucleotide exchange factor, triggering small GTPase signaling and activating phosphorylation of the nuclear factor (NF)kappa B/RelA transcription factor to induce immediate early gene expression. In parallel, nuclear ROS are detected by ataxia telangiectasia mutated (ATM), a PI3 kinase activated by ROS, triggering its nuclear export. ATM forms a scaffold with ribosomal S6 kinases, inducing RelA phosphorylation and resulting in transcription-coupled synthesis of type I and type III interferons and CC and CXC chemokines. We propose that ATM and OGG1 are endogenous nuclear ROS sensors that transmit nuclear signals that coordinate with outside-in pattern recognition receptor signaling, regulating the IIR. (C) 2016 S. Karger AG, Basel
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