IFN regulatory factor-1 plays a central role in the regulation of the expression of class I and II MHC genes in vivo.
IFN regulatory factor-1 plays a central role in the regulation of the expression of class I and II MHC genes in vivo.
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DOI：
10.4049/jimmunol.158.9.4260
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发表时间：
1997-05
影响因子：
4.4
通讯作者：
M. Hobart;V. Ramassar;N. Goes;J. Urmson;Philip F. Halloran
中科院分区：
文献类型：
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作者：
M. Hobart;V. Ramassar;N. Goes;J. Urmson;Philip F. Halloran
转录因子干扰素调节因子-1（IRF-1）参与调节I类MHC的体外表达。我们研究了IRF-1与肾脏和其他非淋巴器官中MHC表达之间的体内关系，评估了IRF-1基因受损小鼠（IRF-1 KO）与IRF-1基因完整小鼠（WT）的MHC表达。在IRF-1 KO小鼠的肾脏中，基础I类表达降低，特别是在动脉内皮上，但基础II类表达不变。与WT小鼠相比，IRF-1科斯中注射rIFN-γ诱导的I类和II类表达均降低。类似地，诱导内源性IFN-γ产生的刺激（LPS或恶唑酮）大量增加WT小鼠肾脏中的MHC表达，而在IRF-1 KO小鼠中几乎没有增加。IRF-1 KO小鼠中rIFN-γ的II类诱导受损可能反映了IRF-1在调节II类反式激活因子（CIITA）表达中的作用：IRF-1 KO小鼠肾脏中rIFN-γ诱导的CIITA mRNA低于WT小鼠。在WT小鼠的器官中，IRF-1 mRNA在基础状态下表达，rIFN-γ处理在I类或CIITA mRNA诱导之前增加IRF-1 mRNA。用放线菌酮加rIFN-γ处理WT小鼠超诱导IRF-1 mRNA表达，但部分抑制CIITA mRNA表达，表明IRF-1 mRNA诱导不依赖于新蛋白质合成，不像CIITA。因此，在体内，IRF-1在基础和诱导的I类表达中以及在IFN-γ诱导II类中起主要作用，可能通过CIITA诱导。
Transcription factor interferon regulatory factor-1 (IRF-1) is implicated in regulating class I MHC expression in vitro. We investigated the in vivo relationship between IRF-1 and MHC expression in kidney and other nonlymphoid organs, assessing MHC expression in mice with disrupted IRF-1 genes (IRF-1 KO) compared with mice with intact IRF-1 genes (WT). In kidneys of IRF-1 KO mice, basal class I expression was decreased, particularly on arterial endothelium, but basal class II expression was unchanged. The induction of both class I and class II expression by injected rIFN-gamma was reduced in IRF-1 KOs, compared with WT mice. Similarly, stimuli that induce endogenous IFN-gamma production (LPS or oxazolone) massively increased MHC expression in kidneys of WT mice, with little increase in IRF-1 KO mice. Impaired class II induction by rIFN-gamma in IRF-1 KO mice probably reflects the role of IRF-1 in regulating class II transactivator (CIITA) expression: rIFN-gamma induced CIITA mRNA less in kidneys of IRF-1 KO mice than in WT mice. In organs of WT mice, IRF-1 mRNA was expressed in the basal state, and rIFN-gamma treatment increased IRF-1 mRNA before the induction of class I or CIITA mRNA. Treatment of WT mice with cycloheximide plus rIFN-gamma superinduced IRF-1 mRNA expression, but partially inhibited CIITA mRNA expression, indicating that IRF-1 mRNA induction is not dependent on new protein synthesis, unlike CIITA. Thus, in vivo, IRF-1 plays a major role in basal and induced class I expression and in induction of class II by IFN-gamma, probably via CIITA induction.