Enhanced B7-2 gene expression by interferon-γ in human monocytic cells is controlled through transcriptional and posttranscriptional mechanisms
Enhanced B7-2 gene expression by interferon-γ in human monocytic cells is controlled through transcriptional and posttranscriptional mechanisms
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DOI：
10.1182/blood.v94.5.1782.417a04_1782_1789
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发表时间：
1999-09-01
期刊：
影响因子：
20.3
通讯作者：
Espinoza-Delgado, I
中科院分区：
文献类型：
--
作者：
Curiel, RE;Garcia, CS;Espinoza-Delgado, I
B7-2是在专职抗原呈递细胞上表达的共刺激分子，其为T细胞提供导致T细胞活化的关键信号。干扰素-γ（IFN-γ）增强单核细胞中B7-2蛋白的表达。然而，控制B7-2表达增强的分子机制知之甚少。北方印迹和流式细胞术分析显示，人单核细胞和人单核细胞系MonoMac 6（MM 6）组成性表达B7-2 mRNA和蛋白，并且IFN-γ处理进一步增强了这两种分子的表达。IFN-γ增强B7-2 mRNA的能力在31 U/mL的剂量下是明显的，并且在500 U/mL时达到平台水平。IFN-γ对B7-2 mRNA表达的影响是时间依赖性的，在处理后3小时内发生，并在24小时内增加。体外转录测定和mRNA稳定性实验表明，IFN-γ增加B7-2 mRNA的转录活性和稳定性。用放线菌酮处理MM 6细胞表明，IFN-γ增强B7-2 mRNA的表达不需要从头蛋白质合成。总之，这些研究首次表明，IFN-γ增强的B7-2蛋白在人单核细胞中的表达是通过涉及转录和转录后机制的双重机制在基因水平上控制的。(C)1999年，美国血液学会。
B7-2 is a costimulatory molecule expressed on professional antigen presenting cells that provides T cells with a critical signal resulting in T-cell activation. Interferon-gamma (IFN-gamma) enhances B7-2 protein expression in monocytic cells. However, the molecular mechanisms controlling the enhanced expression of B7-2 are poorly understood. Northern blot and flow cytometry analysis revealed that human monocytes and the human monocytic cell line MonoMac6 (MM6) constitutively expressed B7-2 mRNA and protein and IFN-gamma treatment further enhanced the expression of both molecules. The ability of IFN-gamma to enhance B7-2 mRNA was evident at the dose of 31 U/mL and reached plateau levels at 500 U/mL. The effects of IFN-gamma on B7-2 mRNA expression were time dependent and occurred within 3 hours of treatment and increased through 24 hours. In vitro transcription assays and mRNA stability experiments showed that IFN-gamma increases both transcriptional activity and the stability of B7-2 mRNA. Treatment of MM6 cells with cycloheximide showed that de novo protein synthesis was not required for the IFN-gamma-enhanced expression of B7-2 mRNA. Overall, these studies show for the first time that IFN-gamma-enhanced expression of B7-2 protein in human monocytic cells is controlled at the gene level through a dual mechanism involving transcriptional and posttranscriptional mechanisms. (C) 1999 by The American Society of Hematology.