Selective apoptosis during treatment with superantigen and lipopolysaccharide
| Project/Area Number |
14571726
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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 |
Morphological basic dentistry
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
RIKIISHI Hidemi Tohoku Univ., Graduate Sch.Dent., Assistant Prof., 大学院・医学系研究科, 講師 (70091767)
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| Co-Investigator(Kenkyū-buntansha) |
AKITA Hirotoshi Tohoku Univ., Graduate Sch.Dent., Assistant Prof., 大学院・医学系研究科, 助手 (10108540)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Superantigen / Lipopolysaccharide / Apoptosis / CD80 / Gingival tissue / Fas / FasL / NF-κB / Cytokine / LPS / カスパーゼ |
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| Research Abstract |
Studies of the events triggered by bacterial superantigens and lipopolysaccharide (LPS) provide rich insight into the constant battle between microbes and the oral immune system. In this study, we demonstrated a mechanism of apoptosis induced by staphylococcal enterotoxin B (SEB) in cultured monocytes and gingival fibroblasts, and some evidence for the anti-apoptotic function in CD80^+ monocytes. Apoptosis of monocytes was accelerated and enhanced by the addition of SEB. Increases in soluble CD95 ligand (sCD95L) levels were observed with stimulation with SEB, but not gamma interferon (IFN-γ). Our results clearly demonstrated that SEB treatment induces the activation of caspase-3 and -8, and pretreatment with zVAD-FMK, a broad inhibitor of caspases, prevented the induction of apoptosis at 24 h. Monocytes expressed constitutive NF-κB binding activity, and SEB further activated NF-κB, which was inhibited by pretreatment with pyrrolidine dithiocarbamate even at dose of 5 μM. PDTC markedly stimulated apoptosis induced by SEB and induced apoptosis in those treated with IFN-γ. Marked inhibition of the appearance of CD80^+ monocytes was achieved by treating cells with zVAD-FMK and DEVD-FMK, which was paralleled by reduced apoptosis of monocytes. LPS treatment resulted in significant reduction of the percentage of SEB-or IFN-γ induced apoptosis through induction of anti-apoptotic protein XIAP. Thus, our results indicated that SEB stimulation includes both anti-apoptotic actions through NF-κB activation and pro-apoptotic actions through sCD95L released by SEB, and that CD80 driven by NF-κB allows gingival tissues to participate in distinct survival programs.
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Report
(3 results)
Research Products
(11 results)
