IFN-γ-dependent transcription of MHC class IIIA is impaired in macrophages from aged mice
IFN-γ-dependent transcription of MHC class IIIA is impaired in macrophages from aged mice
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DOI：
10.1172/jci11696
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发表时间：
2001-02-01
影响因子：
15.9
通讯作者：
Celada, A
中科院分区：
文献类型：
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作者：
Herrero, C;Marqués, L;Celada, A
为了确定年龄对IFN-γ诱导的MHC II类抗原表达的影响，我们在体外产生了骨髓源性巨噬细胞。在这些条件下，我们分析了衰老对巨噬细胞基因组表达的影响，而不受可能受衰老影响的其他细胞类型的影响。虽然从年轻和老年小鼠的巨噬细胞表现出相同程度的分化，与IFN-γ孵育后，在IA复合物的细胞表面的表达和IA β蛋白和mRNA的水平在老年巨噬细胞较低。此外，IA β基因的转录在老年巨噬细胞中受损。在老年巨噬细胞中，与IA β启动子基因的W盒和X盒结合而不与Y盒结合的转录因子的量较低。在IFN-γ处理年轻和老年巨噬细胞后，发现CIITA mRNA水平相似。这表明，在IFN-γ与受体相互作用后开始的初始级联反应和参与CIITA表达的第二信号在老化的巨噬细胞中均未受损。这些数据表明，由于转录受损，衰老与IFN-γ诱导的低水平MHC II类基因相关。
To determine the effect of aging on IFN-gamma -induced MHC class II antigen expression, we produced bone marrow-derived macrophages in vitro. In these conditions, we analyzed the effect of aging on the genomic expression of macrophages without the influence of other cell types that may be affected by aging. Although macrophages from young and aged mice showed an identical degree of differentiation, after incubation with IFN-gamma, the expression at the cell surface of the IA complex and the levels of IA beta protein and mRNA were lower in aged macrophages. Moreover, the transcription of the IA beta gene was impaired in aged macrophages, The amount of transcription factors that bound to the W and X, but not to the Y, boxes of the IA beta promoter gene was lower in aged macrophages. Similar levels of CIITA mRNA were found after IFN-gamma treatment of both young and aged macrophages. This shows that neither the initial cascade that starts after the interaction of IFN-gamma with the receptor nor the second signals involved in the expression of CIITA are impaired in aged macrophages. These data indicate that aging is associated with low levels of MHC class II gene induction by IFN-gamma because of impaired transcription.