MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Narimatsu, M.
Right arrow Articles by Hirano, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Narimatsu, M.
Right arrow Articles by Hirano, T.

Molecular and Cellular Biology, October 2001, p. 6615-6625, Vol. 21, No. 19
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.19.6615-6625.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Tissue-Specific Autoregulation of the stat3 Gene and Its Role in Interleukin-6-Induced Survival Signals in T Cells

Masahiro Narimatsu,1,dagger Hisoka Maeda,1 Shousaku Itoh,1 Toru Atsumi,1 Takuya Ohtani,2 Keigo Nishida,1 Motoyuki Itoh,1,Dagger Daisuke Kamimura,1 Sung-Joo Park,1 Katsunori Mizuno,1 Jun-ichi Miyazaki,3 Masahiko Hibi,1 Katsuhiko Ishihara,1 Koichi Nakajima,2 and Toshio Hirano1,*

Department of Molecular Oncology1 and Department of Nutrition and Physiological Chemistry,3 Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, and Department of Immunology, Osaka City University Graduate School of Medicine, Osaka 545-8485,2 Japan

Received 7 March 2001/Returned for modification 21 May 2001/Accepted 2 July 2001

Signal transducer and activator of transcription 3 (STAT3) mediates signals of various growth factors and cytokines, including interleukin-6 (IL-6). In certain IL-6-responsive cell lines, the stat3 gene is autoregulated by STAT3 through a composite IL-6 response element in its promoter that contains a STAT3-binding element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in the SBE (stat3mSBE). The intact SBE was crucial for IL-6-induced stat3 gene activation in the spleen, especially in the red pulp region, the kidney, and both mature and immature T lymphocytes. The SBE was not required, however, for IL-6-induced stat3 gene activation in hepatocytes. T lymphocytes from the stat3mSBE/mSBE mice were more susceptible to apoptosis despite the presence of IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent activation of the Pim-1 and junB genes, direct target genes for STAT3, was attenuated in T lymphocytes of the stat3mSBE/mSBE mice. Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells.


* Corresponding author. Mailing address: Department of Molecular Oncology (C7), Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-3880. Fax: 81-6-6879-3889. E-mail: hirano{at}molonc.med.osaka-u.ac.jp.

dagger Present address: Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan.

Dagger Present address: Unit on Vertebrate Neural Development, Laboratory of Molecular Genetics, NICHD/NIH, Bethesda, MD 20892.


Molecular and Cellular Biology, October 2001, p. 6615-6625, Vol. 21, No. 19
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.19.6615-6625.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.