| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910;
Department of Medicine, Washington Hospital Center, Washington, DC 20010; and
Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27257
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by diverse cellular and biochemical aberrations, including decreased production of IL-2. Here we show that nuclear extracts from unstimulated SLE T cells, unlike extracts from normal T cells, express increased amounts of phosphorylated cAMP-responsive element modulator (p-CREM) that binds the -180 site of the IL-2 promoter. Nuclear extracts from stimulated normal T cells display increased binding of phosphorylated cAMP-responsive element binding protein (p-CREB) to the -180 site of the IL-2 promoter, whereas nuclear extracts from stimulated SLE T cells display primarily p-CREM and decreased p-CREB binding. In SLE T cells, p-CREM bound to the transcriptional coactivators, CREB binding protein and p300. Increased expression of p-CREM correlated with decreased production of IL-2. The transcription of a reporter gene driven by the -180 site was enhanced in normal T cells, but was suppressed in SLE T cells. These experiments demonstrate that transcriptional repression is responsible for the decreased production of IL-2 by SLE T cells.
This article has been cited by other articles:
|
|
 |
|
  K. Tenbrock, Y.-T. Juang, V. C. Kyttaris, and G. C. Tsokos Altered signal transduction in SLE T cells Rheumatology, October 1, 2007; 46(10): 1525 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, R. A. Barke, and S. Roy Transcriptional and Epigenetic Regulation of Interleukin-2 Gene in Activated T Cells by Morphine J. Biol. Chem., March 9, 2007; 282(10): 7164 - 7171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. C. Kyttaris, Y. Wang, Y.-T. Juang, A. Weinstein, and G. C. Tsokos Increased Levels of NF-ATc2 Differentially Regulate CD154 and IL-2 Genes in T Cells from Patients with Systemic Lupus Erythematosus J. Immunol., February 1, 2007; 178(3): 1960 - 1966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V C Kyttaris, Y Wang, Y-T Juang, A Weinstein, and G C Tsokos cAMP response element modulator {alpha} expression in patients with systemic lupus erythematosus Lupus, December 1, 2006; 15(12): 840 - 844. [Abstract] [PDF]
|
|
|
|
|
|
K. Tenbrock, Y.-T. Juang, N. Leukert, J. Roth, and G. C. Tsokos The Transcriptional Repressor cAMP Response Element Modulator {alpha} Interacts with Histone Deacetylase 1 to Repress Promoter Activity J. Immunol., November 1, 2006; 177(9): 6159 - 6164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Cismasiu, S. Ghanta, J. Duque, D. I. Albu, H.-M. Chen, R. Kasturi, and D. Avram BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes Blood, October 15, 2006; 108(8): 2695 - 2702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Solomou, K. Keyvanfar, and N. S. Young T-bet, a Th1 transcription factor, is up-regulated in T cells from patients with aplastic anemia Blood, May 15, 2006; 107(10): 3983 - 3991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tenbrock, V. C. Kyttaris, M. Ahlmann, J. M. Ehrchen, M. Tolnay, H. Melkonyan, C. Mawrin, J. Roth, C. Sorg, Y.-T. Juang, et al. The Cyclic AMP Response Element Modulator Regulates Transcription of the TCR {zeta}-Chain J. Immunol., November 1, 2005; 175(9): 5975 - 5980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Krishnan, J. G. Kiang, C. U. Fisher, M. P. Nambiar, H. T. Nguyen, V. C. Kyttaris, B. Chowdhury, V. Rus, and G. C. Tsokos Increased Caspase-3 Expression and Activity Contribute to Reduced CD3{zeta} Expression in Systemic Lupus Erythematosus T Cells J. Immunol., September 1, 2005; 175(5): 3417 - 3423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Zielinski, S. N. Jacob, F. Bouzahzah, B. E. Ehrlich, and J. Craft Naive CD4+ T Cells from Lupus-Prone Fas-Intact MRL Mice Display TCR-Mediated Hyperproliferation Due to Intrinsic Threshold Defects in Activation J. Immunol., April 15, 2005; 174(8): 5100 - 5109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. C. Kyttaris, Y.-T. Juang, K. Tenbrock, A. Weinstein, and G. C. Tsokos Cyclic Adenosine 5'-Monophosphate Response Element Modulator Is Responsible for the Decreased Expression of c-fos and Activator Protein-1 Binding in T Cells from Patients with Systemic Lupus Erythematosus J. Immunol., September 1, 2004; 173(5): 3557 - 3563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Elliott, R. A. Shanks, I. U. Khan, J. W. Brooks, P. J. Burkett, B. J. Nelson, V. Kyttaris, Y.-T. Juang, G. C. Tsokos, and G. M. Kammer Down-Regulation of IL-2 Production in T Lymphocytes by Phosphorylated Protein Kinase A-RII{beta} J. Immunol., June 15, 2004; 172(12): 7804 - 7812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V C Kyttaris, Y-T Juang, and G C Tsokos Gene therapy in systemic lupus erythematosus Lupus, May 1, 2004; 13(5): 353 - 358. [Abstract] [PDF]
|
|
|
|
|
|
S. Krishnan, D. L. Farber, and G. C. Tsokos T Cell Rewiring in Differentiation and Disease J. Immunol., October 1, 2003; 171(7): 3325 - 3331. [Full Text] [PDF]
|
|
|
|
|
|
M. P. Nambiar, C. U. Fisher, A. Kumar, C. G. Tsokos, V. G. Warke, and G. C. Tsokos Forced Expression of the Fc Receptor {gamma}-Chain Renders Human T Cells Hyperresponsive to TCR/CD3 Stimulation J. Immunol., March 15, 2003; 170(6): 2871 - 2876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tenbrock, Y.-T. Juang, M. Tolnay, and G. C. Tsokos The Cyclic Adenosine 5'-Monophosphate Response Element Modulator Suppresses IL-2 Production in Stimulated T Cells by a Chromatin-Dependent Mechanism J. Immunol., March 15, 2003; 170(6): 2971 - 2976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Juang, K. Tenbrock, M. P. Nambiar, M. F. Gourley, and G. C. Tsokos Defective Production of Functional 98-kDa Form of Elf-1 Is Responsible for the Decreased Expression of TCR {zeta}-Chain in Patients with Systemic Lupus Erythematosus J. Immunol., November 15, 2002; 169(10): 6048 - 6055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tenbrock, Y.-T. Juang, M. F. Gourley, M. P. Nambiar, and G. C. Tsokos Antisense Cyclic Adenosine 5'-Monophosphate Response Element Modulator Up-Regulates IL-2 in T Cells from Patients with Systemic Lupus Erythematosus J. Immunol., October 15, 2002; 169(8): 4147 - 4152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Juang, E. E. Solomou, B. Rellahan, and G. C. Tsokos Phosphorylation and O-Linked Glycosylation of Elf-1 Leads to Its Translocation to the Nucleus and Binding to the Promoter of the TCR {zeta}-Chain J. Immunol., March 15, 2002; 168(6): 2865 - 2871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D W Montgomery Prolactin production by immune cells Lupus, October 1, 2001; 10(10): 665 - 675. [Abstract] [PDF]
|
|
|
|
|
|
E. E. Solomou, Y.-T. Juang, and G. C. Tsokos Protein Kinase C-{{theta}} Participates in the Activation of Cyclic AMP-Responsive Element-Binding Protein and Its Subsequent Binding to the -180 Site of the IL-2 Promoter in Normal Human T Lymphocytes J. Immunol., May 1, 2001; 166(9): 5665 - 5674. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
