| Project/Area Number |
18591128
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
SAITO Kazuyoshi University of Occupational and Environmental Health, Japan, School of Medicine, associate professor (30279327)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAOKA Kunihiro University of Occupational&Environmental Health, School of Medicine, assistant professor (20425317)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | IL1 beta / inflammatory cytokine / transcriptional factor / transcriptional regulation |
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| Research Abstract |
Prolonged production of inflammatory cytokines including IL-lb from monocytes/ macrophages in the tissue is a major pathological feature of Rheumatoid Arthritis (RA). Regarding the transcriptional regulation of IL-lb gene, we revealed the importance of promoter sequences immediately upstream of the transcription start site (cap site) and identified the element located position between-3134 and -2729 was required for maximal LPS and PMA induction. The enhancer region also involved in the increase transcription of IL-lb gene in human monocytic cell line THP-1, murine macrophage cell line RAW 267.4 cells as well as-RA synovial cells, synovial cell line Ell. Using a serial CAT plasmid including these mitogen responsive elements, we also found negative regulatory region located between-2833 and-2782. The deletion of the element resulted in the augmentation of transcription of IL-lb gene in both THP-1 and RAW 267.4 cells but not in Ell. We conducted electrophoretic mobility shift assay using 32P-labeled oligonucleotides of the negative regulatory element. A single band was enhanced by LPS, PMA stimulation and not competed by antibodies for conventional transcriptional factors including jun and fos families and NFkB.
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