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脂多糖低反应性小鼠腹腔巨噬细胞中干扰素β mRNA 周转的选择性改变及其在自发性干扰素表达缺陷中的作用

Selective alteration of the turnover of interferon beta mRNA in peritoneal macrophages from LPS-hyporesponsive mice and its role in the defective expression of spontaneous interferon.

作者信息

Gessani S, Dieffenbach C W, Conti L, DiMarzio P, Wilson K L, Belardelli F

机构信息

Department of Virology, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Virology. 1993 Mar;193(1):507-9. doi: 10.1006/viro.1993.1154.

DOI:10.1006/viro.1993.1154
PMID:8438587
Abstract

Basal levels of interferon (IFN)-beta mRNA transcription were detected in both freshly explanted LPS-responsive (Lpsn) and LPS-hyporesponsive (Lpsd) peritoneal macrophages (PM). In vitro cultivation of PM resulted in a time-dependent reduction in the level of IFN-beta mRNA, which was far more rapid in Lpsd than in Lpsn PM. Treatment of Lpsn PM with cycloheximide (CHX) resulted in a marked accumulation of IFN-beta mRNA, which was not associated with an increase in IFN-beta gene transcription. However, treatment of Lpsd PM with CHX did not induce accumulation of IFN-beta mRNA. CHX induced the accumulation of IFN-alpha-4 mRNA in both Lpsn and Lpsd PM, CHX enhanced the accumulation of two cytoplasmic factors interacting with AU-rich sequences within the 3' untranslated region of IFN-beta mRNA. We conclude that Lpsd PM exhibit an impaired capacity to stabilize IFN-beta mRNA that may account for their low expression of IFN-beta.

摘要

在新鲜分离的对脂多糖(LPS)有反应(Lpsn)和对LPS反应低下(Lpsd)的腹腔巨噬细胞(PM)中均检测到干扰素(IFN)-β mRNA转录的基础水平。PM的体外培养导致IFN-β mRNA水平呈时间依赖性降低,Lpsd中的降低速度比Lpsn PM快得多。用环己酰亚胺(CHX)处理Lpsn PM导致IFN-β mRNA显著积累,这与IFN-β基因转录增加无关。然而,用CHX处理Lpsd PM并未诱导IFN-β mRNA积累。CHX诱导Lpsn和Lpsd PM中IFN-α-4 mRNA积累,CHX增强了两种与IFN-β mRNA 3'非翻译区内富含AU序列相互作用的细胞质因子的积累。我们得出结论,Lpsd PM稳定IFN-β mRNA的能力受损,这可能是其IFN-β低表达的原因。

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Interferon gamma upregulates its own gene expression in mouse peritoneal macrophages.干扰素γ上调其在小鼠腹腔巨噬细胞中的自身基因表达。
J Exp Med. 1994 May 1;179(5):1731-6. doi: 10.1084/jem.179.5.1731.