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J Neuroimmunol. 2002 Jan;122(1-2):74-84.

Interferon regulatory factor-1 is required for interferon-gamma-induced MHC class I genes in astrocytes.

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  • 1Department of Microbiology and Immunology, State University of New York Upstate Medical University, 750 East Adams St., Syracuse, NY 13210, USA.


Recent studies have shown that the role of the transcription factor interferon regulatory factor-1 (IRF-1) in the expression of major histocompatibility complex (MHC) class I molecules is tissue-specific. Our previous studies indicated a role for IRF-1 in expression of MHC class I genes in cultured astrocytes in response to interferon-gamma (IFN-gamma). However, the requirement for IRF-1 in MHC class I expression has not been directly analyzed in neural tissue. To further ascertain the importance of IRF-1 in the induction of MHC class I genes in astrocytes in response to IFN-gamma, we analyzed astrocytes from mice with a targeted disruption of the IRF-1 gene (IRF-1(-/-) mice). As expected, astrocytes from wild type (IRF-1(+/+)) mice showed a coordinate increase in both IRF-1 and MHC class I gene expression in response to IFN-gamma. To the contrary, astrocytes from IRF-1(-/-) mice had greatly reduced MHC class I mRNA expression. MHC class I gene promoter activity in astrocytes was controlled entirely through a single enhancer, the MHC-IRF-E, to which IRF-1 bound in response to IFN-gamma in wild type but not in IRF-1(-/-) mouse astrocytes. In vivo, astrocytes in brains of wild type mice readily responded to IFN-gamma to express MHC class I molecules. This correlated with increased MHC class I mRNA in the brain. In contrast, brains of IRF-1(-/-) mice showed no MHC class I gene induction following exposure to IFN-gamma indicating that all cells in the central nervous system (CNS) including astrocytes with the potential to express MHC class I molecules were dependent on IRF-1. These studies conclusively demonstrate a major role for IRF-1/MHC-IRF-E interactions in controlling MHC class I gene expression in astrocytes in response to IFN-gamma.

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