1993 Fiscal Year Final Research Report Summary
Transcriptional regulation of cytokine genes in rheumatic diseases.
| Project/Area Number |
04807047
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | University of Occupational and Environmental Health, School of Medicine |
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Principal Investigator |
SHIRAKAWA Fumihiko UOEH,School of Medicine, Assistant Professor, 医学部, 講師 (10158967)
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| Co-Investigator(Kenkyū-buntansha) |
OTA Toshiyuki UOEH,School of Medicine, Associate Professor, 医学部, 助教授 (10140930)
ETO Sumiya UOEH,School of Medicine, Professor, 医学部, 教授 (90010347)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Rheumatic deseases / Rheumatoid arthritis / Synovial cells / Cytokine / Interleukin / Transcription / Promoter / Enhancer |
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| Research Abstract |
In rheumatic arthritis (RA), cytokines such as interleukin (IL) -1beta and IL-6 are overproduced and are involved in the synovial proliferation and joint destruction. In this study, the regulational mechanism of IL-1beta and IL-6 gene transcription was studied by using RA synovial cells. IL-1beta or IL-6 upstream DNA regions were ligated with a reporter gene, chroramphenicol acetyltransferase (CAT). IL-beta and IL-6 CAT plasmids were transfected into cells and transcriptional activities were evaluted by CAT assay. Both of the IL-1beta and IL-6 regulatory genes were active in these cells. Furthermore, IL-1 protein stimulated IL-1beta and IL-6 regulatory genes. Tax gene of HTLV-1, one of the retroviruses which are recenty suggested to evoke RA-like synovitis, was transfected into these cells. Tax gene makedly transactivated IL-1beta and IL-6 genes. Deletion and point mutation analysis in CAT experiments and band shift assays showed that a transcriptional nuclear factor, NF-kB was essential in cytokine gene transctivation by tax gene. These results suggested that NF-kB may be one of the most important nuclear factors in IL-1beta and IL-6 gene transcription in RA.
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