2001 Fiscal Year Final Research Report Summary
Inhibition of superantigen-induced apoptosis by LPS
| Project/Area Number |
12671759
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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 Univerisity, Graduate Sch. Dent., Assistant Prof., 大学院・歯学研究科, 講師 (70091767)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAWARA Shunji Tohoku Univerisity, Graduate Sch. Dent., Assistant Prof., 大学院・歯学研究科, 助手 (10241639)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Superantigen / LPS / Apoptosis / CD80 / Monocyte / Fas / Fas L |
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| Research Abstract |
Studies of the events triggered by bacterial superantigens provide rich insight into the constant battle between microbes and the immune system. In this study, we demonstrated a mechanism of apoptosis induced by staphylococcal enterotoxin B (SEB) in monocytes and some evidence for the anti-apoptotic function in CD80^+ monocytes. Pretreatment with pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-κB, resulted in significant reduction of the percentages of SEB-and IFN-γ (produced by SEB)-induced CD80^+ monocytes. Monocytes expressed constitutive NF-κB binding activity, and SEB and IFN-γ further activated NF-κB, which was inhibited by pretreatment with PDTC. Apoptosis of monocytes was enhanced by the addition of SEB. Increases in soluble CD95 ligand (sCD95L) levels were observed following stimulation with SEB, but not IFN-γ. Our results demonstrated that SEB treatment induced the activation of caspase-3 and -8, and pretreatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases, prevented the induction of apoptosis at 24 h. CD80^- monocytes were sensitive to apoptosis, and survival of CD80^- monocytes from apoptosis by treating with z-VAD-fmk resulted in reduction of the percentages of CD80^+ monocytes. PDTC abolished anti-apoptotic function in those treated with IFN-γ. Thus, our results indicated that SEB stimulation includes both anti-apoptotic action through NF-κB activation by IFN-γ and pro-apoptotic action through sCD95L released by SEB, and that CD80 driven by NF-κB allows monocytes to participate in distinct survival programs and massive T-cell activation.
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