| Project/Area Number |
11671675
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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 |
Otorhinolaryngology
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| Research Institution | Fukui Medical University |
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Principal Investigator |
FUJIEDA Shigeharu Fukui medical University, Lecture, 医学部・附属病院, 講師 (30238539)
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| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | oligodeoxynucleotides / CpG motif / IgE / MY-1 / IFN-γ / IL-12 / palindromic sequence / human B cells / 合成DNA / PBMC / IL-4 / anti-CD40 |
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| Research Abstract |
Syhthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs have the capacity to stimulate Th-1 responses in mice. Th-1 cytokines are known to act as down-regulators of IgE production. In this study we investigated whether synthetic ODNs inhibited IgE production in human PBMC from normal donors stimulated with interleukin-4 (IL-4) plus anti-CD40 monoclonal antibody (mAb) in vitro. Thirty-mer single-stranded ODNs were randomly selected from the cDNA encoding the MPB-70 of Mycobacterium bovis BCG.Two ODNs containing CGTACG or AAGGTT inhibited IgE production by human PBMC.When a portion of the sequence of the core or flanking oligonucleotides in the ODN containing CGTACG was substituted with other oligonucleotides, ODNs containing NACGTTCG or A/CTCGTTCG equences specifically inhibited the IgE production of human PBMC in vitro. The inhibition of IgE production by certain ODN was mediated by both IFNγ and IL-12, since the ODN-induced suppression was blocked by the addition of anti-IFNγ or anti-IL-12 mAb. Also, the ODNs inhibited the induction of the ε germ-line transcript by IL-4. Our findings indicate that the administration of synthetic ODNs appears to be a therapeutic candidate for the treatment of IgE-dependent allergic disease in humans.
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