2004 Fiscal Year Final Research Report Summary
Study for roles of IL-18 in interstitial lung diseases and lung remodeling
| Project/Area Number |
15390261
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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 |
Respiratory organ internal medicine
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| Research Institution | Kurume University |
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Principal Investigator |
HOSHINO Tomoaki Kurume University, Department of Internal Medicine 1, Assistant Professor, 医学部, 助手 (00261066)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Interstitial Lung Diseases / Cytokine / IL-18 / Caspase-1 / Mouse Model / thioredoxin |
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| Research Abstract |
Rationale : Administration of several chemotherapeutic drugs such as bleomycin, busulfan, and gefitinib often induces lethal lung injury. IL-1β and IL-18, members of the IL-1 family, are produced from a biologically inactive precursor and secreted from macrophages after cleavage by caspase-1. We established a new mouse model for human interstitial lung diseases in which daily administration of IL-18 with IL-2 induced lethal lung injury. Recently, we reported an increased level of IL-18 and IL-18Rα expression in the lungs of patients with idiopathic pulmonary fibrosis. Objectives : The aim of our present study was to evaluate the roles of IL-1β and IL-18 in the pathogenesis of bleomycin-induced lung injury. Methods : We investigated whether IL-1R and IL-18 secretion induced by bleomycin causes lung injury in caspase-1 deficient (-/-), IL-18 (-/-), and IL-18Ra (-/-) mice, and in humans. Measurement and Main Results: Intravenous administration of bleomycin induced the expression of IL-1β, IL-18, and various cytokines and chemokines (e.g. MIP-2, IP-10, MCP-1, and TCA-3) in the serum and lungs of normal mice. Macrophages (Kupffer cells) isolated from wild-type mice, but not caspase-1 (-/-) mice, secreted IL-1βand IL-18 upon stimulation with bleomycin in vitro. Bleomycin-induced lung injury was prevented in caspase-1 (-/-), IL-18 (-/-), and IL-18Rα (-/-) mice, but not in control mice. Moreover, enhanced expression of IL-18 and IL-18Rα was observed in the lungs of patients with bleomycin-induced lung injury. Conclusions : Our results suggest IL-1β and IL-18 secretion in the lungs may cause severe lung injury as a consequence of treatment with some chemotherapeutic drugs.
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Research Products
(15 results)
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[Journal Article] Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis2004
Author(s)
Kitasato Y, Hoshino T, Okamoto M, Kato S, Koda Y, Nagata N, Kinoshita M, Koga H, Yoon DY, Asao H, Ohmoto H, Koga T, Rikimaru T, Aizawa H.
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Journal Title
Am J Respir Cell Mol Biol 31
Pages: 619-625
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism2004
Author(s)
Matsumoto K, Inoue H, Nakano T, Tsuda M, Yoshiura Y, Fukuyama S, Tsushima F, Hoshino T, Aizawa H, Akiba H, Pardoll D, Hara N, Yagita H, Azuma M, Nakanishi Y.
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Journal Title
J Immunol 172
Pages: 2530-2541
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice.2003
Author(s)
Ishikura T, Kanai T, Uraushihara K, Iiyama R, Makita S, Totsuka T, Yamazaki M, Sawada T, Nakamura T, Miyata T, Kitahora T, Hibi T, Hoshino T, Watanabe M.
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Journal Title
J Gastroenterol Hepatol 18
Pages: 960-969
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bone malformations in interleukin-18 transgenic mice2003
Author(s)
Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Nakamura M, Maeda Y, Nishiwaki E, Zenmyo M, Hiraoka K, Aizawa H, Yoshino K.
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Journal Title
J Bone Miner Res 18
Pages: 975-983
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted Interleukin-18 Expression in the Skin.2003
Author(s)
Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kirii Y, Nishiwaki E, Maeda Y, Takeda J, Okamoto M, Kato S, Imaizumi T, Aizawa H, Yoshino K
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Journal Title
J Invest Dermatol 121
Pages: 502-509
Description
「研究成果報告書概要(欧文)」より
