Therapeutic Approach for Allergic or Autoimmune Diseases by Modulation of CD25+CD4+ T Cells
| Project/Area Number |
13670863
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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 |
Dermatology
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| Research Institution | Tohoku University |
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Principal Investigator |
AIBA Setsuya Tohoku University, Graduate School of Medicine, Professor, 医学部附属病院, 助手 (00271940)
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| Co-Investigator(Kenkyū-buntansha) |
相場 節也 東北大学, 大学院・医学系研究科, 教授 (80159269)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Dendritic Cells / Ultraviolet / MAP Kinase / Apoptosis / Tolerance / ヒト |
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| Research Abstract |
Although ultraviolet B (UVB) induces apoptosis and functional perturbations in dendritic cells (DCs), e.g. Langerhans cells (LCs), it also stimulates some LCs into maturation after irradiation in vivo. To analyze its reciprocal effects on DCs, we elucidated the direct effect of UVB on DCs in vitro using human monocyte-derived DCs (MoDCs). UVB from 50 to 200 J/m^2 stimulated the maturation of MoDCs with 1) augmented expression of co-stimulatory molecules such as CD86 and HLA-DR, 2) enhanced production of IL-1β, IL-6, IL-8, IL-10 and TNF-α at both the mRNA and protein levels, and 3) enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses induced apoptotic cell death. Western-blot analysis of MoDCs after UVB demonstrated a dose-dependent phosphorylation of p38-and c-JUN N-terminal kinase (JNK)-mitogen-activated protein kinases (MAPKs), but not that of extracellular signal-regulated kinases (ERK). P38 MAPK-inhibitor, SB203580, inhibited both UVB-induced maturation and apoptosis of MoDCs. Interestingly, MoDCs that had undergone apoptosis exhibited an augmented expression of HLA-DR without up-regulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our study revealed a dual effect of UVB, to stimulate maturation or to induce apoptosis in MoDCs, depending on the dosage, mainly via the p38 MAPK-pathway.
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Report
(3 results)
Research Products
(1 results)
