Abstract
Despite a key role in the regulation of interferon (IFN) gene expression and in mediating many downstream actions of the IFNs, the regulation of IFN regulatory factor (IRF) gene expression in the normal and pathological central nervous system and, indeed, other tissues, is poorly defined. We sought to examine the expression and regulation of the IRF genes in a number of different murine models for immune- or virally induced central nervous system disease. Here, we describe the development of a multiprobe RNase protection assay that permits the simultaneous detection and quantification of IRF ribonucleic acid transcripts for multiple family members in murine cells and tissues.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Barnes, B., Lubyova, B., and Pitha, P. M. (2002) On the role of IRF in host defense. J. Interferon Cytokine Res. 22, 59ā71.
Levy, D. E., Marie, I., and Prakash, A. (2003) Ringing the interferon alarm: differential regulation of gene expression at the interface between innate and adaptive immunity. Curr. Opin. Immunol. 15, 52ā58.
Navikas, V. and Link, H. (1996) Review: Cytokines and the pathogenesis of multiple sclerosis. J. Nuerosci. Res. 45, 322ā333.
Benveniste, E. N. (1998) Cytokine actions in the central nervous sytem. Cytokine Growth Factor Rev. 9, 259ā275.
Huang, X., Yuang, J., Goddard, A., Foulis, A., James, R. F., Lernmark, A., et al. (1995) Interferon expression in the pancreases of patients with type I diabetes. Diabetes 44, 658ā64.
Lebon, P., Badoual, J., Ponsot, G., Goutieres, F., Hemeury-Cukier, F., and Aicardi, J. (1988) Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy. J. Neurol. Sci. 84, 201ā208.
Taniguchi, T., Ogasawara, K., Takaoka, A., and Tanaka, N. (2001) IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 19, 623ā655.
Grandvaux, N., tenOever, B., Servant, M. J., and Hiscott, J. (2002) The interferon antiviral response: from viral invasion to evasion. Curr. Opin. Infect. Dis. 15, 259ā267.
Nehyba, J., Hrdlickova, R., Burnside, J., and Bose, H. R. J. (2002) A novel interferon regulatory facotr (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein. Mol. Cell. Biol. 22, 3942ā3957.
Qin, B. Y., Liu, C., Lam, S. S., Sumpter, R., Jr., Ikeda, M., Lemon, S. M., and Gale, M., Jr. (2003) Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation. Nat. Struct. Biol. 10, 913ā921.
Foy, E., Li, K., Wang, C., Sumpter, R., Jr., Ikeda, M., Lemon, S. M., and Gale, M., Jr. (2003) Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300, 1145ā1148.
Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G. P., Lin, R., and Hiscott, J. (2003) Triggering the interferon antiviral response through an IKK-related pathway. Science 300, 1148ā1151.
Levy, D. E., Marie, I., Smith, E., and Prakash, A. (2002) Enhancement and diversification of IFN induction by IRF-7-mediated positive feedback. J. Interferon Cytokine Res. 22, 87ā93.
Stalder, A., Pagenstecher, A., Kincaid, C., and Campbell, I. L. (1999) Analysis of gene expression by multiprobe RNase protection assay, in Neurodegeneration Methods and Protocols. (Harry, J., and Tilson, H. A., eds.), Humana Press, Totowa, NJ, pp. 53ā66.
Dudov, K. P. and Perry, R. P. (1984) The gene family encoding the mouse ribosomal protein L32 contains a uniquely expressed intron-containing gene and an unmutated processed gene. Cell 37, 457ā468.
Badley, J. E., Bishop, G. A., St. John, T., and Frelinger, J. A. (1988) A simple, rapid method for the purification of poly A+ RNA. Biotechniques. 6, 114ā116.
Campbell, I. L., Hobbs, M. V., Kemper, P., and Oldstone, M. B. A. (1994) Cerebral expression of multiple cytokine genes in mice with lymphocytic choriomeningitis. J. Immunol. 152, 716ā723.
Lassmann, S., Kincaid, C., Asensio, V. C., and Campbell, I. L. (2001) Induction of type I immune pathology in the brain following immunization without central nervous system autoantigen in transgenic mice with astrocyte-targeted expression of IL-12. J. Immunol. 167, 5485ā5493.
Akwa, Y., Hassett, D. E., Eloranta, M. L., Sandberg, K., Masliah, E., Powell, H., Whitton, J. L., Bloom, F. E., and Campbell, I. L. (1998) Transgenic expression of IFN-Ī± in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration. J. Immunol. 161, 5016ā5026.
Pagenstecher, A., Lassmann, S., Carson, M. J., Kincaid, C. L., Stalder, A. K., and Campbell, I. L. (2000) Astrocyte-targeted expression of IL-12 induces active cellular immune responses in the central nervous system and modulates experimental allergic encephalomyelitis. J. Immunol. 164, 4481ā4492.
Acknowledgments
This study was supported by NIH grants MH62231; MH62261 and NS36979 to I.L.C. S.O. is a postdoctoral fellow of the National Multiple Sclerosis Society (NMSS) and Multiple Sclerosis Society of Canada. This is manuscript number 16320-NP from the Scripps Research Institute.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2005 Humana Press Inc.
About this protocol
Cite this protocol
Ousman, S.S., Campbell, I.L. (2005). Regulation of Murine Interferon Regulatory Factor Gene Expression in the Central Nervous System Determined by Multiprobe RNase Protection Assay. In: Carr, D.J.J. (eds) Interferon Methods and Protocols. Methods in Molecular Medicineā¢, vol 116. Humana Press. https://doi.org/10.1385/1-59259-939-7:115
Download citation
DOI: https://doi.org/10.1385/1-59259-939-7:115
Publisher Name: Humana Press
Print ISBN: 978-1-58829-418-0
Online ISBN: 978-1-59259-939-4
eBook Packages: Springer Protocols