IFN-γ–dependent transcription of MHC class II IA is impaired in macrophages from aged mice
Carmen Herrero, … , Jorge Lloberas, Antonio Celada
Carmen Herrero, … , Jorge Lloberas, Antonio Celada
Published February 15, 2001
Citation Information: J Clin Invest. 2001;107(4):485-493. https://doi.org/10.1172/JCI11696.
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IFN-γ–dependent transcription of MHC class II IA is impaired in macrophages from aged mice

Abstract

To determine the effect of aging on IFN-γ–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-γ, the expression at the cell surface of the IA complex and the levels of IAβ protein and mRNA were lower in aged macrophages. Moreover, the transcription of the IAβ 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 IAβ promoter gene was lower in aged macrophages. Similar levels of CIITA mRNA were found after IFN-γ treatment of both young and aged macrophages. This shows that neither the initial cascade that starts after the interaction of IFN-γ 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-γ because of impaired transcription.

Authors

Carmen Herrero, Laura Marqués, Jorge Lloberas, Antonio Celada

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Figure 1

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Similar size and antigen Mac1 expression in macrophages from aged and yo...
Similar size and antigen Mac1 expression in macrophages from aged and young mice. In each case, macrophages were prepared from the bone marrow of pools of five young (6-week-old) or five aged (24-month-old) mice. The size of macrophages was determined by cytometry. Surface expression of Mac1 (CD11b) was assessed by cytometry using specific antibodies after blocking the Fc receptors. In some experiments, macrophages were treated for 24 hours with M-CSF (1200 U/ml) or IFN-γ (300 U/ml). The first two panels are representative of six independent experiments. In the third panel, data are represented as the mean ± SD of six experiments. No significant differences were found between young and aged macrophages (P > 0.05).