title: Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells.
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 (stat3(mSBE)). 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 stat3(mSBE/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 stat3(mSBE/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.
authors.affiliation: Department of Molecular Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Narimatsu
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
authors.forename: T
authors.initials: T
authors.lastname: Ohtani
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: D
authors.initials: D
authors.lastname: Kamimura
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: M
authors.initials: M
authors.lastname: Hibi
authors.forename: K
authors.initials: K
authors.lastname: Ishihara
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: T
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D018390:Gene Targeting; D015850:Interleukin-6 / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D015533:Transcriptional Activation; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D001616:beta-Galactosidase