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

By Masahiro Narimatsu, Hisoka Maeda, Shousaku Itoh, Toru Atsumi, Takuya Ohtani, Keigo Nishida, Motoyuki Itoh, Daisuke Kamimura, Sung-Joo Park, Katsunori Mizuno, Jun-ichi Miyazaki, Masahiko Hibi, Katsuhiko Ishihara, Koichi Nakajima and Toshio Hirano

Abstract

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

Topics: Cell Growth and Development
Publisher: American Society for Microbiology
Year: 2001
DOI identifier: 10.1128/MCB.21.19.6615-6625.2001
OAI identifier: oai:pubmedcentral.nih.gov:99807
Provided by: PubMed Central
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