The Journal of Immunology, Vol 150, Issue 8 3300-3310, Copyright © 1993 by American Association of Immunologists

ARTICLES

Regulation of MHC class I and beta 2-microglobulin gene expression in human neuronal cells. Factor binding to conserved cis-acting regulatory sequences correlates with expression of the genes

PD Drew, M Lonergan, ME Goldstein, LA Lampson, K Ozato and DE McFarlin
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.

MHC class I molecules are coexpressed with beta 2-microglobulin (beta 2- M) on many somatic cells. However, these proteins are normally not present on cells of the central nervous system (CNS). Cells derived from human neuroblastomas were used as a model for investigating the molecular basis for the paucity of MHC class I and beta 2-M gene expression in neural cells and for the induction of these genes by two cytokines, IFN-gamma, and TNF-alpha. These cytokines independently increased MHC class I and beta 2-M cell surface expression on the neuroblastoma cell lines. IFN-gamma or TNF-alpha also increased MHC class I and beta 2-M steady-state RNA levels and the expression of MHC class I and beta 2-M CAT reporter constructs transiently transfected into the neuroblastoma cell lines, indicating that the cytokines acted by increasing the transcription of these genes. MHC class I and beta 2- M genes share two conserved regulatory elements, an NF kappa B-like site and the IFN consensus sequence, that act as a constitutive enhancer and an IFN-responsive element, respectively. Low MHC class I and beta 2-M gene expression in these cells was accounted for by undetectable to low factor binding activity specific for the above regulatory elements of these genes. TNF-alpha increased factor binding activity specific for the NF kappa B-like elements and IFN-gamma increased factor binding activity specific for the IFN consensus sequence elements of the MHC class I and beta 2-M genes, but not vice versa. Taken together, our results indicated that IFN-gamma and TNF- alpha increased MHC class I and beta 2-M gene expression in the neuroblastoma cell lines by inducing factor binding to the regulatory elements present in both genes.

This article has been cited by other articles:

				Y. Choi, G. A. Johnson, T. E. Spencer, and F. W. Bazer Pregnancy and Interferon Tau Regulate Major Histocompatibility Complex Class I and {beta}2-Microglobulin Expression in the Ovine Uterus Biol Reprod, May 1, 2003; 68(5): 1703 - 1710. [Abstract] [Full Text] [PDF]

				P. F. Halloran, M. Afrouzian, V. Ramassar, J. Urmson, L.-F. Zhu, L. M. H. Helms, K. Solez, and N. M. Kneteman Interferon-{{gamma}} Acts Directly on Rejecting Renal Allografts to Prevent Graft Necrosis Am. J. Pathol., January 1, 2001; 158(1): 215 - 226. [Abstract] [Full Text] [PDF]

				T. Kimura and D. E. Griffin The Role of CD8+ T Cells and Major Histocompatibility Complex Class I Expression in the Central Nervous System of Mice Infected with Neurovirulent Sindbis Virus J. Virol., July 1, 2000; 74(13): 6117 - 6125. [Abstract] [Full Text]

				C. A. Salkowski, K. Kopydlowski, J. Blanco, M. J. Cody, R. McNally, and S. N. Vogel IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice J. Immunol., August 1, 1999; 163(3): 1529 - 1536. [Abstract] [Full Text] [PDF]

				S. Dhib-Jalbut, J. Xia, H. Rangaviggula, Y.-Y. Fang, and T. Lee Failure of Measles Virus to Activate Nuclear Factor-{kappa}B in Neuronal Cells: Implications on the Immune Response to Viral Infections in the Central Nervous System J. Immunol., April 1, 1999; 162(7): 4024 - 4029. [Abstract] [Full Text] [PDF]

				O A Khan, H Jiang, P S Subramaniam, H M Johnson, and S S Dhib-Jalbut Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders Multiple Sclerosis, April 1, 1998; 4(2): 63 - 69. [Abstract] [PDF]

				H. Neumann, H. Schmidt, A. Cavalie, D. Jenne, and H. Wekerle Major Histocompatibility Complex (MHC) Class I Gene Expression in Single Neurons of the Central Nervous System: Differential Regulation by Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha J. Exp. Med., January 20, 1997; 185(2): 305 - 316. [Abstract] [Full Text] [PDF]

				C. Murphy, D. Nikodem, K. Howcroft, J. D. Weissman, and D. S. Singer Active Repression of Major Histocompatibility Complex Class I Genes in a Human Neuroblastoma Cell Line J. Biol. Chem., November 29, 1996; 271(48): 30992 - 30999. [Abstract] [Full Text] [PDF]

				M. Bickel, S.M. Nothen, K. Freiburghaus, and D. Shire Chemokine Expression in Human Oral Keratinocyte Cell Lines and Keratinized Mucosa Journal of Dental Research, November 1, 1996; 75(11): 1827 - 1834. [Abstract] [PDF]