| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Promoter Function in Disease Due to an Intracellular Pathogen1
,
,,
Departments of
*
Microbiology and Immunology,
Medicine, and
Biochemistry, and
Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler, TX 75708;
¶ National Institute of Aging, National Institutes of Health, Baltimore, MD 21224;
||
Crippled Children’s Foundation Research Center, Le Bonheur Children’s Hospital, and Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103;
#
Department of Internal Medicine, University of North Texas Health Sciences Center, Fort Worth, TX 76107;
**
Inflammatory Bowel Disease Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
Department of Immunology and Microbiology, University of Miami School of Medicine, Miami, FL 33124; and
*
Laboratory of Experimental Immunology, National Cancer Institute at Frederick, Frederick, MD 21702
Mycobacterium tuberculosis-induced IFN-
protein
and mRNA expression have been shown to be reduced in tuberculosis
patients, compared with healthy tuberculin reactors. To determine
whether this decrease was associated with reduced activity of the
IFN- promoter, we first studied binding of nuclear proteins to the
radiolabeled proximal IFN- promoter (-71 to -40 bp), using EMSAs
with nuclear extracts of freshly isolated peripheral blood T cells.
Nuclear extracts of T cells from most tuberculosis patients showed
markedly reduced expression of proteins that bind to the proximal
IFN- promoter, compared with findings in nuclear extracts of T cells
from healthy tuberculin reactors. These DNA-binding complexes contained
CREB proteins, based on competitive EMSAs, supershift assays, and
Western blotting with an anti-CREB Ab. Transient transfection of
PBLs with a luciferase reporter construct under the control of the
IFN- promoter revealed reduced IFN- promoter activity in
tuberculosis patients. Transient transfection of Jurkat cells with a
dominant-negative CREB repressor plasmid reduced IFN- promoter
activity. These data suggest that reduced expression of CREB nuclear
proteins in tuberculosis patients results in decreased IFN- promoter
activity and reduced IFN- production.
This article has been cited by other articles:
|
|
 |
|
  X. Wang, P. F. Barnes, K. M. Dobos-Elder, J. C. Townsend, Y.-t. Chung, H. Shams, S. E. Weis, and B. Samten ESAT-6 Inhibits Production of IFN-{gamma} by Mycobacterium tuberculosis-Responsive Human T Cells J. Immunol., March 15, 2009; 182(6): 3668 - 3677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Samten, J. C. Townsend, S. E. Weis, A. Bhoumik, P. Klucar, H. Shams, and P. F. Barnes CREB, ATF, and AP-1 Transcription Factors Regulate IFN-{gamma} Secretion by Human T Cells in Response to Mycobacterial Antigen J. Immunol., August 1, 2008; 181(3): 2056 - 2064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Samten, J. C. Townsend, Z. Sever-Chroneos, V. Pasquinelli, P. F. Barnes, and Z. C. Chroneos An antibody against the surfactant protein A (SP-A)-binding domain of the SP-A receptor inhibits T cell-mediated immune responses to Mycobacterium tuberculosis J. Leukoc. Biol., July 1, 2008; 84(1): 115 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Pang and S. T. Howard Regulation of the {alpha}-Crystallin Gene acr2 by the MprAB Two-Component System of Mycobacterium tuberculosis J. Bacteriol., September 1, 2007; 189(17): 6213 - 6221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Pang, P. Vu, T. F. Byrd, S. Ghanny, P. Soteropoulos, G. V. Mukamolova, S. Wu, B. Samten, and S. T. Howard Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis Microbiology, April 1, 2007; 153(4): 1229 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Colmone, S. Li, and C.-R. Wang Activating Transcription Factor/cAMP Response Element Binding Protein Family Member Regulated Transcription of CD1A J. Immunol., November 15, 2006; 177(10): 7024 - 7032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Samten, S. T. Howard, S. E. Weis, S. Wu, H. Shams, J. C. Townsend, H. Safi, and P. F. Barnes Cyclic AMP Response Element-Binding Protein Positively Regulates Production of IFN-{gamma} by T Cells in Response to a Microbial Pathogen J. Immunol., May 15, 2005; 174(10): 6357 - 6363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yano, P. Ghosh, H. Kusaba, M. Buchholz, and D. L. Longo Effect of Promoter Methylation on the Regulation of IFN-{gamma} Gene During In Vitro Differentiation of Human Peripheral Blood T Cells into a Th2 Population J. Immunol., September 1, 2003; 171(5): 2510 - 2516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Samten, B. Wizel, H. Shams, S. E. Weis, P. Klucar, S. Wu, R. Vankayalapati, E. K. Thomas, S. Okada, A. M. Krensky, et al. CD40 Ligand Trimer Enhances the Response of CD8+ T Cells to Mycobacterium tuberculosis J. Immunol., March 15, 2003; 170(6): 3180 - 3186. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
