Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Park, W.-R.
Right arrow Articles by Fujiwara, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, W.-R.
Right arrow Articles by Fujiwara, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

International Immunology, Vol. 16, No. 2, pp. 295-302, February 2004
© 2004 Japanese Society for Immunology

A mechanism underlying STAT4-mediated up-regulation of IFN-{gamma} induction inTCR-triggered T cells

Woong-Ryeon Park1, Masakiyo Nakahira1, Naotoshi Sugimoto1, Yang Bian1, Yumi Yashiro-Ohtani1, Xu-Yu Zhou1, Yi-Fu Yang1, Toshiyuki Hamaoka1 and Hiromi Fujiwara1

1 Department of Oncology (C6), Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan

Correspondence to: H. Fujiwara; E-mail: hf{at}ongene.med.osaka-u.ac.jp
Transmitting editor: T. Saito

IL-12 promotes Th1 development/IFN-{gamma} expression by activating STAT4. However, it is still unclear how STAT4 elicits IFN-{gamma} promoter activation. Here, we investigated the mechanism by which IL-12-activated STAT4 functions for IFN-{gamma} induction in TCR-triggered T cells. TCR stimulation induced high levels of IFN-{gamma} production depending on co-stimulation with IL-12. IL-12 stimulation greatly enhanced the promoter-binding activity of c-Jun/AP-1, a critical transcription factor for IFN-{gamma} gene expression in wild-type T cells, but not in STAT4-deficient (STAT4–/–) T cells. Comparable amounts of c-Jun were induced by TCR stimulation in both wild-type and STAT4–/– T cells irrespective of IL-12 co-stimulation. However, c-Jun bound to STAT4 in IL-12-co-stimulated wild-type T cells. c-Jun forming a complex with STAT4 efficiently interacted with the AP-1-related sequence of the IFN-{gamma} promoter. Such an enhanced c-Jun binding did not occur in STAT4–/– T cells. These results show that STAT4 contributes to enhancing IFN-{gamma} expression by up-regulating the binding of TCR signal-induced AP-1 to the relevant promoter sequence.

Keywords: cytokine, signal transduction, transcription factor


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
P. R. Mittelstadt, H. Yamaguchi, E. Appella, and J. D. Ashwell
T Cell Receptor-mediated Activation of p38{alpha} by Mono-phosphorylation of the Activation Loop Results in Altered Substrate Specificity
J. Biol. Chem., June 5, 2009; 284(23): 15469 - 15474.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. T. O'Malley, R. D. Eri, G. L. Stritesky, A. N. Mathur, H.-C. Chang, H. HogenEsch, M. Srinivasan, and M. H. Kaplan
STAT4 Isoforms Differentially Regulate Th1 Cytokine Production and the Severity of Inflammatory Bowel Disease
J. Immunol., October 1, 2008; 181(7): 5062 - 5070.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. R. Ortaldo, R. Winkler-Pickett, J. Wigginton, M. Horner, E. W. Bere, A. T. Mason, N. Bhat, J. Cherry, M. Sanford, D. L. Hodge, et al.
Regulation of ITAM-positive receptors: role of IL-12 and IL-18
Blood, February 15, 2006; 107(4): 1468 - 1475.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.