論文 - 詳細
| RRC ID | 12208 |
|---|---|
| 著者 | Miyazawa K, Mori A, Yamamoto K, Okudaira H. |
| タイトル | Transcriptional roles of CCAAT/enhancer binding protein-beta, nuclear factor-kappaB, and C-promoter binding factor 1 in interleukin (IL)-1beta-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes. |
| ジャーナル | J Biol Chem |
| Abstract |
The involvement of interleukin (IL)-6 in the pathogenesis of rheumatoid arthritis (RA) has been recently demonstrated. IL-1beta stimulated rheumatoid fibroblast-like synoviocytes (FLSs) to produce IL-6 in a concentration- and time-dependent manner. In the present study we investigated how the IL-6 promoter is transcriptionally regulated in rheumatoid FLSs in response to a physiologically relevant mediator of inflammation, IL-1beta. Deletion analysis showed that the IL-6 promoter is regulated by two positive elements (located at -159 to -142 base pairs (bp) and -77 to -59 bp). Electrophoretic mobility shift assays revealed that CCAAT/enhancer binding protein-beta (C/EBPbeta) binding to nucleotides -159 to -142 bp was constitutively present. The probe corresponding to nucleotides -77 to -59 bp gave three positive bands. The two slower migrating bands were induced by IL-1beta and comprised an nuclear factor (NF)-kappaB p50/p65 heterodimer and a p65/p65 homodimer. The faster migrating band was constitutively expressed and identified as Epstein-Barr virus C-promoter binding factor 1, CBF1. Site-specific mutagenesis analysis demonstrated that the NF-kappaB and CBF1 binding elements regulated inducible activity of the IL-6 promoter in response to IL-1beta stimulation, whereas the C/EBPbeta binding element mainly regulated basal activity. We also provide the first evidence that CBF1 functions as a positive regulator of human IL-6 gene transcription. |
| 巻・号 | 273(13) |
| ページ | 7620-7 |
| 公開日 | 1998-3-27 |
| DOI | 10.1074/jbc.273.13.7620 |
| PII | S0021-9258(18)61738-7 |
| PMID | 9516466 |
| MeSH | Arthritis, Rheumatoid / metabolism* CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins / metabolism* Fibroblasts / metabolism Gene Expression Regulation / drug effects Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein Interleukin-1 / pharmacology* Interleukin-6 / biosynthesis* Interleukin-6 / genetics NF-kappa B / metabolism* Nuclear Proteins / metabolism* Promoter Regions, Genetic Recombinant Proteins / metabolism Synovial Membrane / cytology Synovial Membrane / drug effects Synovial Membrane / metabolism* Transcription Factors / metabolism* Transcription, Genetic |
| IF | 4.238 |
| 引用数 | 68 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 遺伝子材料 | pGEMhIL-6 GT (RDB01211) |