Role of IL/25 in the regulation of allergic airway inflammation
Project/Area Number |
15590797
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | CHIBA UNIVERSITY |
Principal Investigator |
IWAMOTO Itsuo Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10111436)
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Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Hiroshi Chiba University Hospital, Assistant Professor, 医学部附属病院, 助手 (00322024)
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Project Period (FY) |
2003 – 2004
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Project Status |
Completed (Fiscal Year 2004)
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Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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Keywords | IL-25 / Mast cells / IL-17 / Eosinophils / Th2 cells / 好酸球 / Th2細胞 |
Research Abstract |
Recently, cytokines homologous to IL-17 have been identified by database searching. Five new family members have been identified, namely IL-17B,IL-17C,IL-17D,IL-17E/IL-25,and IL-17F, in which these molecules possess 18-30% homology to IL-17. Among IL-17 family cytokines, it has been shown that the in vivo and in vitro biological activities of IL-25 are markedly different from those described for IL-17 and other IL-17 family cytokines. The expression of IL-25 results in the expansion of eosinophils through the production of IL-5 from an unidentified non-T cell population, whereas other IL-17 family cytokines induce the expansion of neutrophils. In addition, IL-25 induces elevated gene expression of IL-4 and IL-13 in multiple tissues and the resultant Th2-type immune responses, including increased serum IgE levels and pathological changes with eosinophilic infiltrates. In the present study, we first show that mast cells are also potent IL-25-producing cells. We found that when bone marrow-derived mast cells(BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min in a calcineurin-dependent manner and the levels of IL-25 mRNA were comparable to that of activated Th2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting. We also investigated the role of IL-25 in allergic airway inflammation. We found that IL-25 mRNA was induced in the airways in the sensitized mice upon the inhaled allergen challenge. Moreover, the enforced expression of IL-25 in the lung in CC10-IL-25 transgenic mice resulted in the enhanced antigen-induced airway inflammation. These results suggest that IL-25 is involved in the enhancement of allergic airway inflammation.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Proteolytic processing of Stat6 signaling in mast cells as a negative-regulatory mechanism.2002
Author(s)
Nakajima H, Suzuki K, Kagami S-i, Suto A, Ikeda K, Hirose K, Hiwasa T, Takeda K, Saito Y, Akira S, Iwamoto I.
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Journal Title
J.Exp.Med. 196
Pages: 27-38
Description
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