2005 Fiscal Year Final Research Report Summary
Analysis of IL-18-induced type-1 bronchial asthma
| Project/Area Number |
16390291
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
YOSHIMOTO Tomohiro Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60241171)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Nobuki Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (90368514)
YASUDA Koubun Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (50333539)
NAKANISHI Kenji Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (60172350)
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| Project Period (FY) |
2004 – 2005
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| Keywords | bronchial asthma / IL-18 / Th1 cells / airway hyperresponsiveness / IL-13 / IFN-γ / infection |
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| Research Abstract |
IL-18 was originally regarded to induce Th1-related cytokines. In general, factors favoring IFN-γ production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their relevant role in induction of bronchial asthma. Administration of Ag induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were co-administered with IL-18. Furthermore, mice having received IFN-γ-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR following intranasal administration of Ag and IL-18. Thus, Th1 cells become very harmful cells when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-γ-expressing Th1 cells, both of which express IL-18Rα chain strongly, produce IFN-γ, IL-9, IL-13, GM-CSF, TNF-α, RANTES and MIP-1α upon stimulation with Ag, IL-2 and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.
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Research Products
(19 results)
