| Project/Area Number |
17590444
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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 |
Immunology
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
HAYASHI Nobuki Hyogo College of Medicine, Faculty pf Medicine, Part-time teacher, 医学部, 非常勤講師 (90368514)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMOTO Tomohiro Hyogo College of Medicine, Faculty pf Medicine, Assosiate Professor, 医学部, 助教授 (60241171)
TSUTSUI Hiroko Hyogo College of Medicine, Faculty pf Medicine, Professor, 医学部, 教授 (40236914)
NAKANISHI Kenji Hyogo College of Medicine, Faculty pf Medicine, Professor, 医学部, 教授 (60172350)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | IL-18 / Th1 cells / airway hyperresponsiveness / Th1 cell-induced bronchial / lung fibrosis asthma |
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| Research Abstract |
We previously reported that OVA and IL-18 nasally administered act on memory type Thl cells to induce airway hyper responsiveness (AHR) and inflammation, characterized by per ibronchial infiltration with neutrophils and eosinophils. In this study, we have investigated this administration also induces lung fibrosis in an IL-13-dependent manner. Thl cells secrete several cytokines including IFN-g and bronchogenic cytokine IL-13, when stimulated with Ag and IL-18. However, IL-13 blockade failed to attenuate AHR, although this treatment inhibited eosinophilic infiltration. To understand the mechanism how Th1cells induce AHR following Ag plus IL-18 challenge, we have established passive and active Th1 mice by transferring OVA-specific Th1 cells into or OVA/CFA immunization of naive BALB/c mice, respectively. Administration of Ag and IL-18 induced both types of Th1 mice to develop AHR, airway inflammation and lung fibrosis. Neutralization of IL-13 or IFN-g during Ag plus IL-18 challenges inhibited eosinophilic infiltration/lung fibrosis/periostin deposition or neutrophilic infiltration/AHR, respectively. We also found co-administration of OVA and LPS into Th1 mice induced AHR and airway inflammation via endogenous IL-18.Neutralization of IL-18 or IFN-g attenuated AHR and decreased the number of neutrophils in BALF. These results clearly indicated that endogenous IL-18 plays a critical role in induction of this mouse model of bronchial asthma.Thus, IL-18 becomes a key target molecule to develop therapeutic regimen for the treatment of Th1 cell-induced bronchial asthma.
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