| Project/Area Number |
11670450
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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 |
内科学一般
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| Research Institution | Kyushu University |
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Principal Investigator |
OTSUKA Takeshi Kyushu University Graduate School of Medical Sciences, assistant professor, 医学部附属病院, 助手 (50213773)
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| Co-Investigator(Kenkyū-buntansha) |
NIIRO Hiroaki Kyushu University, 特別研究員
SHIMODA Kazuya Kyushu University Graduate School of Medical Sciences, assistant professor, 医学部附属病院, 助手 (90311844)
NAKASHIMA Hitoshi Kyushu University Graduate School of Medical Sciences, assistant professor, 医学部附属病院, 助手 (70188960)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | macrophage / neutrophil / interleukin-4 / interleukin-10 / cyclooxygenase / CD40 / signal transduction / rheumatoid arthritis / proinflammatory cytokines / polymorphism / ミクロオキシゲナーゼ / シグナル伝達 |
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| Research Abstract |
(monocytes/macrophages)
CD40 expression of human peripheral blood monocytes (PBMs) was enhanced in the presence of IFN-g, and further induction was achieved by GM-CSF.So far, signaling cascades of CD40 have been examined by using the cells expressing CD40L on their cell membrane. We used anti CD40 antibody as a stimulant, and it was strong enough to induce PBMNs productions of both TNFa and PGE2. These results indicated that CD40 signaling does not need an interaction of other costimulatory molecules. Induced PGE2 production was accompanied by the induction of COX-2 on the level of gene expression. Both MAP Kinases and NFkBwere activated by CD40L-CD40 interaction, although their activation profiles were different from those stimulated by LPS.
(neutrophils)
In LPS-stimulated human neutrophils, the activation of ERK and p38 MAPK is independently involved in the induction of COX-2 protein, and in PGE2 synthesis. LPS induces the phosphorylation and activation of ERK2 and p38 MAPK in neutrophi
… More
ls.
Both IL-4 and IL-10 completely inhibited LPS-induced COX-2 expression and PGE2 synthesis in neutrophils. Neither of these cytokines alone induced the phosphorylation or activation of these Kinases. Interestingly, IL-10 partly inhibited LPS-induced phosphorylation and activation of p38 MAPK, although IL-4 did not affect LPS-induced phosphorylation or activation of p38 MAPK.In addition, LPS-induced phosphorylation and activation of ERK2 was not affected at all by these cytokines. These results suggest that LPS-induced phosphorylation and activation of p38 MAPK was partly regulated by IL-10, but not by IL-4.
Activation of peripheral blood monocytes and neutrophils of patients with rheumatoid arthritis (RA) should be different from those stimulated with LPS in vitro. PGE2 production by RA neutrophils was higher than that by normal neutrophils, and it was chiefly carried out by cyclooxygenase (COX)-2. By using inhibitors for MAP kinase cascade, RA neutrophils showed the activation both of ERK2 and p38 MAPK.IL-4, IL-10 or dexamethasone were able to suppress LPS-induced but not constitutively elevated PGE2 production in RA neutrophils. These results addressed the question that activated condition of RA neutrophils is different from that of neutrophils stimulated by LPS. Less
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