Elucidation of leukotriene B4 receptor 1, BLT1-dependent immune response by dendritic cells and neutrophils
| Project/Area Number |
15K19032
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kumamoto University (2016)
Juntendo University (2015) |
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Principal Investigator |
KOGA TOMOAKI 熊本大学, 大学院先導機構, 助教 (30615092)
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| Co-Investigator(Renkei-kenkyūsha) |
Yokomizo Takehiko 順天堂大学, 医学部・生化学第一講座, 教授 (60302840)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 生理活性脂質 / 好中球 / 樹状細胞 / GPCR / ロイコトリエンB4 / BLT1 / リピドミクス / RAGE / LTB4 / LTA4H / コンディショナルノックアウト |
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| Outline of Final Research Achievements |
In the present study, we investigated the role of LTB4-BLT1 axis in neutrophils and dendritic cells. We found that BLT1 interacts with receptor for advanced glycation end products (RAGE), which is important receptor for the regulation of various chronic inflammatory diseases including diabetes, atherosclerosis, Alzheimer's diseases and etc. We also showed that RAGE enhances LTB4-BLT1-dependent neutrophil migration in vitro and in vivo through the activation of MEK-ERK signaling pathway. RAGE is known to be up-regulated by aging, so it might be possible that BLT1 signaling is exaggerated by aging through RAGE induction in vivo. If we can inhibit RAGE, we might also inhibit LTB4-BLT1 signaling, and subsequent infiltration of neutrophils into inflammatory area. We therefore propose RAGE as a novel therapeutic target for various inflammatory diseases by targeting LTB4-BLT1 signaling.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity.2017
Author(s)
Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo M, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N.
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Journal Title
Cancer Discov
Volume: in press
Issue: 5
Pages: 522-538
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Inhibition of Leukotriene B4 Action Mitigates Intracerebral Hemorrhage-Associated Pathological Events in Mice2017
Author(s)
Hijioka, M., Anan, J., Ishibashi, H., Kurauchi, Y., Hisatsune, A., Seki, T., Koga, T., Yokomizo, T., Shimizu, T.,Katsuki, H.
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Journal Title
J Pharmacol Exp Ther
Volume: 360
Issue: 3
Pages: 399-408
DOI
Related Report
Peer Reviewed
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[Journal Article] Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury2016
Author(s)
Shigematsu, M., Koga, T., Ishimori, A., Saeki, K., Ishii, Y., Taketomi, Y., Ohba, M., Jo-Watanabe, A., Okuno, T., Harada, N., Harayama, T., Shindou, H., Li, J. D., Murakami, M., Hoka, S.,Yokomizo, T.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 34560-34560
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Endoplasmic Reticulum (ER) Stress Induces Sirtuin 1 (SIRT1) Expression via the PI3K-Akt-GSK3β Signaling Pathway and Promotes Hepatocellular Injury.2015
Author(s)
Koga T, Suico MA, Shimasaki S, Watanabe E, Kai Y, Koyama K, Omachi K, Morino-Koga S, Sato T, Shuto T, Mori K, Hino S, Nakao M, Kai H.
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Journal Title
J Biol Chem.
Volume: 290
Issue: 51
Pages: 30366-30374
DOI
Related Report
Peer Reviewed / Open Access
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