Regulation of IL-18 and IL-38 for the treatment of inflammatory pulmonary diseases
| Project/Area Number |
16K09595
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | IL-38 / 喘息 / 好酸球 / IL-5 / 炎症性肺疾患 / サイトカイン / IL-18 / 気管支喘息マウスモデル / 気管支喘息 / 分子細胞呼吸器学 |
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| Outline of Final Research Achievements |
The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed. The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p<0.05). The number of airway eosinophils in IL-38-KO mice was significantly lower than in WT mice after OVA challenge (p<0.01). BALF analysis confirmed the lower number of airway eosinophils in IL-38-KO mice and showed that this was significantly associated with lower IL-5 protein levels (r=0.92, p<0.0001). However, the additional rm IL-38 protein did not neutralize airway eosinophilia in IL-38-KO mice.IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction.We also reported that IL-18 strongly involves in activation of Macrophage Activation Syndrome（MAS).
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| Academic Significance and Societal Importance of the Research Achievements |
新規IL-1ファミリーサイトカインIL-38は抗炎症性サイトカインの可能性があることが示唆された（Biochemistry and Biophysics Reports 2015）。一方、IL-38は炎症性サイトカインの可能性を本研究で証明した。すなわち、IL-38は抗炎症性と炎症性サイトカインの二つの可能性を本研究で証明した。
申請者は抗ヒトIL-38モノクロナール抗体を樹立した。抗IL-38モノクロナール抗体H127CはBiolegend, eBioscienceから世界中で販売され,IL-38の研究に役立っている。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Association between soluble immune mediators and tumor responses in patients with nonsmall cell lung cancer treated with anti-PD-1 inhibitor.2019
Author(s)
Matsuo N, Azuma K, Hattori S, Ohtake J, Kawahara A, Ishii H, Tokito T, Yamada K, Shibata Y, Shimokawaji T, Kondo T, Kato T, Saito H, Yamada K, Sasada T, Hoshino T.
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Journal Title
Int J Cancer.
Volume: 144
Issue: 5
Pages: 1170-1179
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease.2017
Author(s)
Yoshida N, Okamoto M, Kaieda S, Fujimoto K, Ebata T, Tajiri M, Nakamura M, Tominaga M, Wakasugi D, Kawayama T, Kuwana M, Mimori T, Ida H, Hoshino T
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Journal Title
Respiratory investigation
Volume: 55(1)
Pages: 24-32
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis.2017
Author(s)
Ohta S, Okamoto M, Fujimoto K, Sakamoto N, Takahashi K, Yamamoto H, Kushima H, Ishii H, Akasaka K, Ono J, Kamei A, Azuma Y, Matsumoto H, Yamaguchi Y, Aihara M, Johkoh T, Kawaguchi A, Ichiki M, Sagara H, Kadota JI, Hanaoka M, Hayashi SI, Kohno S, Hoshino T, Izuhara K
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
