論文 - 詳細
RRC ID | 12193 |
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著者 | Miyazawa K, Mori A, Okudaira H. |
タイトル | IL-6 synthesis by rheumatoid synoviocytes is autonomously upregulated at the transcriptional level. |
ジャーナル | J Allergy Clin Immunol |
Abstract |
BACKGROUND:Involvement of IL-6 in the pathogenesis of rheumatoid arthritis has recently been demonstrated, but the mechanism of its production by rheumatoid synoviocytes is still poorly defined. OBJECTIVE:The purpose of this study was to clarify the cellular and molecular mechanisms involved in the spontaneous production of IL-6 by fibroblast-like synoviocytes obtained from patients with rheumatoid arthritis. METHODS:Cloned synoviocytes were established by the limiting dilution method. IL-6 synthesis was evaluated by ELISA and Northern blot analysis. IL-6 gene transcription and transcription factors were analyzed by the transient transfection of luciferase reporter plasmids and the electrophoretic mobility shift assay, respectively. RESULTS:IL-6 synthesis by cloned rheumatoid synoviocytes was spontaneously upregulated at the transcriptional level. Enhanced IL-6 production by high-producing clones was independent of cytokines from other cell populations or autocrine production of tumor necrosis factor-alpha and IL-1. Deletion analysis showed that the IL-6 promoter was regulated by 2 positive elements (-159 to -142 base pair and -77 to -59 base pair). The transcriptional activity of the latter element was upregulated in clones showing high IL-6 production. The binding activity of NF-kappaB p50/p65 heterodimer and RBP-Jkappa was enhanced in these clones. CONCLUSION:IL-6 production by rheumatoid synoviocytes is autonomously upregulated at the transcriptional level and spontaneous activation of NF-kappaB and RBP-Jkappa seems to be involved. |
巻・号 | 103(5 Pt 2) |
ページ | S437-44 |
公開日 | 1999-5-1 |
DOI | 10.1016/s0091-6749(99)70159-4 |
PII | S0091-6749(99)70159-4 |
PMID | 10329846 |
MeSH | Arthritis, Rheumatoid / metabolism* Clone Cells Electrophoresis Fibroblasts / cytology Humans Interleukin-6 / biosynthesis* Interleukin-6 / genetics Interleukin-6 / physiology Osteoarthritis / metabolism Synovial Membrane / cytology* Synovial Membrane / metabolism Transcription, Genetic Up-Regulation |
IF | 10.228 |
引用数 | 20 |
WOS 分野 | ALLERGY IMMUNOLOGY |
リソース情報 | |
遺伝子材料 | pGEMhIL-6 GT Human IL-6 genomic clone (RDB01211) |