| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany; and
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140
{FOOT;f3}
IL-4 is a pleiotropic immunoregulatory cytokine secreted by activated Th2, but not Th1, cells. The proximal IL-4 promoter contains MARE, C/EBP, P0, octamer-like, P1, and activating protein-1 elements. The half c-Maf binding site (MARE), P0, and P1 sites were previously shown to be involved in Th2-specific transcriptional activity. Except the MARE and P1 site, the molecular basis for Th2 specificity of the P0 site has not been analyzed. Here, we provide the first detailed analysis of the P0 binding factors and show that in Th2, but not in Th1, cells, NF-AT and proteins of the activating protein-1 family are involved in cooperative binding to the P0 and the adjacent octamer-like site. In the mouse Th2 D10 cells, Oct-1/Oct-2 are also found to participate in formation of the P0-binding complexes. Mutation, deletion, and methylation interference analysis demonstrate that both the P0 and the octamer-like sequence are required for inducible binding. Furthermore, we provide the first report of the functional relevance of each site in the human IL-4 promoter by mutagenesis/transfection analysis and demonstrate that the octamer-like, P0 and P1 sites are important for the biologic function of the IL-4 promoter. The MARE site, although it was shown to be critical for the function of the murine IL-4 promoter, does not appear essential for human IL-4 promoter activity in Jurkat T cells. These findings suggest that besides c-Maf, another Th2-specific factor(s) may be involved in tissue-specific expression of the IL-4 gene.
This article has been cited by other articles:
|
|
 |
|
  U. De Fanis, F. Mori, R. J. Kurnat, W. K. Lee, M. Bova, N. F. Adkinson, and V. Casolaro GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells Blood, May 15, 2007; 109(10): 4343 - 4350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zeng, X. Zhang, Z. Huang, L. Cheng, S. Yao, D. Qin, X. Chen, Q. Tang, Z. Lv, L. Zhang, et al. Intracellular Tat of Human Immunodeficiency Virus Type 1 Activates Lytic Cycle Replication of Kaposi's Sarcoma-Associated Herpesvirus: Role of JAK/STAT Signaling J. Virol., March 1, 2007; 81(5): 2401 - 2417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ryzhov, A. E. Goldstein, I. Biaggioni, and I. Feoktistov Cross-Talk between Gs- and Gq-Coupled Pathways in Regulation of Interleukin-4 by A2B Adenosine Receptors in Human Mast Cells Mol. Pharmacol., August 1, 2006; 70(2): 727 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nirula, M. Ho, H. Phee, J. Roose, and A. Weiss Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4 J. Exp. Med., July 10, 2006; 203(7): 1733 - 1744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Georas, J. Guo, U. De Fanis, and V. Casolaro T-helper cell type-2 regulation in allergic disease Eur. Respir. J., December 1, 2005; 26(6): 1119 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Hu, S. Y. Jang, J. C. Fanzo, and A. B. Pernis Modulation of T Cell Cytokine Production by Interferon Regulatory Factor-4 J. Biol. Chem., December 13, 2002; 277(51): 49238 - 49246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. F. Schwenger, C. C. Kok, E. Arthaningtyas, M. A. Thomas, C. J. Sanderson, and V. A. Mordvinov Specific Activation of Human Interleukin-5 Depends on de Novo Synthesis of an AP-1 Complex J. Biol. Chem., November 27, 2002; 277(49): 47022 - 47027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takeba, H. Nagafuchi, M. Takeno, J.-i. Kashiwakura, and N. Suzuki Txk, a Member of Nonreceptor Tyrosine Kinase of Tec Family, Acts as a Th1 Cell-Specific Transcription Factor and Regulates IFN-{gamma} Gene Transcription J. Immunol., March 1, 2002; 168(5): 2365 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Andersen and M. G. Rosenfeld POU Domain Factors in the Neuroendocrine System: Lessons from Developmental Biology Provide Insights into Human Disease Endocr. Rev., February 1, 2001; 22(1): 2 - 35. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. A. WIERENGA and G. MESSER Regulation of Interleukin 4 Gene Transcription . Alterations in Atopic Disease? Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): S81 - 85. [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Glimcher and K. M. Murphy Lineage commitment in the immune system: the T helper lymphocyte grows up Genes & Dev., July 15, 2000; 14(14): 1693 - 1711. [Full Text]
|
|
|
|
|
|
C. Cerdan, E. Serfling, and D. Olive The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4+ T cells Blood, July 15, 2000; 96(2): 420 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Hehner, M. Li-Weber, M. Giaisi, W. Droge, P. H. Krammer, and M. L. Schmitz Vav Synergizes with Protein Kinase C{Theta} to Mediate IL-4 Gene Expression in Response to CD28 Costimulation in T Cells J. Immunol., April 1, 2000; 164(7): 3829 - 3836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Kashiwakura, N. Suzuki, H. Nagafuchi, M. Takeno, Y. Takeba, Y. Shimoyama, and T. Sakane Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon {gamma} Production in Human T Lymphocytes J. Exp. Med., October 18, 1999; 190(8): 1147 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Wierenga, M. Walchner, G. Kick, M. L. Kapsenberg, E. H. Weiss, and G. Messer Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients Int. Immunol., February 1, 1999; 11(2): 297 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Q. Cron, S. J. Bort, Y. Wang, M. W. Brunvand, and D. B. Lewis T Cell Priming Enhances IL-4 Gene Expression by Increasing Nuclear Factor of Activated T Cells J. Immunol., January 15, 1999; 162(2): 860 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Li-Weber, M. Giasi, and P. H. Krammer Involvement of Jun and Rel Proteins in Up-regulation of Interleukin-4 Gene Activity by the T Cell Accessory Molecule CD28 J. Biol. Chem., December 4, 1998; 273(49): 32460 - 32466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Guo, V. Casolaro, E. Seto, W.-M. Yang, C. Chang, M.-C. Seminario, J. Keen, and S. N. Georas Yin-Yang 1 Activates Interleukin-4 Gene Expression in T Cells J. Biol. Chem., December 21, 2001; 276(52): 48871 - 48878. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
