| 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
|
| リソース情報 |
| 遺伝子材料 |
pGEMhIL-6 GT (RDB01211) |
