Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3
Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3
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DOI：
10.1016/j.virol.2006.05.034
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发表时间：
2006-09-30
期刊：
影响因子：
3.7
通讯作者：
Petro, Thomas M.
中科院分区：
文献类型：
--
作者：
Dahlberg, Angela;Auble, Mark R.;Petro, Thomas M.
对病毒感染作出反应的巨噬细胞可能导致自身免疫性脱髓鞘疾病（ADD）。与来自ADD抗性B10.S小鼠的巨噬细胞相比，来自对泰勒病毒（TMEV）感染、TLR 7激动剂洛索立宾或TLR 4激动剂LPS应答的ADD易感SJL/J小鼠的巨噬细胞表达较少的IL-12 p35，但表达更多的IL-12/23 p40和IFN-β。虽然B10.S和SJL/J TMEV感染的巨噬细胞之间IRF-1和-7的表达相似，但SJL/J而不是B10.S巨噬细胞表现出组成型活性IRF-3。与刺激p35启动子报告基因活性的过表达IRF-1、IRF-5和IRF-7相反，过表达IRF-3抑制了对TMEV感染、洛索立宾、IFN-γ/LPS的应答的p35启动子活性，但不单独抑制IFN-γ。IRF-3减弱但不消除IRF-1刺激的p35启动子活性。IRF-3的抑制需要p35启动子的-172至-122 bp。这些数据表明，预活化的IRF-3是B10.S和SJL/J巨噬细胞对TMEV应答的IL-12产生差异的主要因素。(c)2006年爱思唯尔公司All rights reserved.
Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-beta than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-gamma/LPS, but not IFN-gamma alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV. (c) 2006 Elsevier Inc. All rights reserved.