A functional analysis and establishment of a therapeutic approach for the selective inhibition of selection-dependent eosinophil recruitment to the skin
| Project/Area Number |
16591091
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
SATOH Takahiro Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院医歯学総合研究科, 助教授 (30235361)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Yasuhiro Tokyo Medical and Dental University, Graduate School, Assistant Professor, 医学部付属病院, 講師 (40302848)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Eosinophils / Selection / Endothelial cells / Fucosyltransferases / STAT6 / Skin inflammation / Fucosyltransferase / Eosinophns / Eosinophil / Endotelial cells / Fuoosyltransferase |
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| Research Abstract |
(1) Contribution of selectin ligands to eosinophil recruitment into the skin.
We examined the relative expression of selectin ligands on human eosinophils using whole blood flow cytometric analysis. Whereas blood eosinophils had little avidity for E-selectin, they clearly bound P-selectin. Human eosinophils expressed a large amount of α(1,3) fucosyltransferase (FT)-IV mRNA, but little or no FT-VII mRNA compared with neutrophils. FT-IV in human eosinophils may be more relevant to the generation of functional P-selectin ligand than FT-VII.
(2) Synthesis of FT-IV- and -VIT-dependent eosinophil selectin ligand and recruitment to the skin.
To define the physiological role of FT-TV and FT-VII in expression of eosinophil selectin ligand, we characterized models of dermal eosinophilia in FT-IV- and/or FT-VII-deficient mice in vivo. FT-IV deficiency yielded a significant decrease in eosinophil recruitment to the skin. Likewise, deficiency of FT-VII also yielded a decrease in eosinophil recruitment. Eosinophil recruitment that remained in the absence of FT-VII was further inhibited by blocking P- or E-selectin and was essentially absent in mice deficient in both enzymes.
(3) P-selectin expression on human dermal endothelial cells.
We demonstrated increased expression of P-selectin in dermal vessels of regional skin in urticaria and atopic dermatitis. The in vitro analyses with human dermal microvascular endothelial cells revealed that histamine rapidly induced P-selectin expression. IL-4, IL-13, and substance P induced prolonged expression of surface P-selectin. Activation of STAT6 appears to be a key factor in P-selectin expression by IL-4 and substance P because STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. STAT6 in dermal endothelial cells appears to be a potent target for controlling eosinophil infiltrate in allergic and/or neuroinflammatory skin diseases.
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] Postaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor2006
Author(s)
Satoh T, 2006 R, 2621 K, Urade Y, Kanai Y, Sumi K, Yokozeki H, Hirai H, Nagata K, Hara T, Utsuyama M, Hirokawa K, Sugamura K, Nishioka K, Nakamura M
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Journal Title
J Immunol 177
Pages: 2621-2629
Description
「研究成果報告書概要(欧文)」より
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