Regulation of bone marrow-derived monocytic cells and inhibition of inflammation-associated colon cancer development by chemokines and neurotransmitters
Project/Area Number |
16K09307
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Mie University |
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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 単球 / 線維細胞 / CCR2 / CX3CR1 / AOM/DSS / 大腸線維化 / 大腸癌 / 大腸炎 / ケモカイン受容体 / 骨髄キメラマウス / 炎症性腸疾患関連大腸癌 / MMP / TIMP-1 / 大腸 / 線維化 / MCP-1 / 単球系細胞 / ケモカイン / 自律神経 |
Outline of Final Research Achievements |
We prepared bone marrow (BM) chimeric mice, which were reconstituted with BM cells derived from CC chemokine receptor 2 (CCR2)-deficient mice or CX3C chemokine receptor 1 (CX3CR1)-deficient mice. After 2 months of BM transplantation, BM chimeric mice were treated with azoxymethane/dextran sodium sulfate (DSS). At 10 days after the third DSS treatment, in CCR2-deficient BM chimeric mice compared with in wild-type (WT) BM chimeric mice, the number of monocytes and fibrocytes in the colonic lamina propria and mRNA expression level of tissue inhibitor of metalloproteinase-1 in the colon tissue were significantly reduced, and colon fibrosis was attenuated by hyper-degradation of extracellular type I collagen. At 10 weeks after the third DSS treatment, shortening of the colon length was dampened and the number of colon tumors was significantly reduced in both CCR2-deficient BM chimeric mice and CX3CR1-deficient BM chimeric mice compared with in WT BM chimeric mice.
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Academic Significance and Societal Importance of the Research Achievements |
炎症性腸疾患患者の診療で重要な課題は、慢性炎症による線維化(大腸の短縮)と大腸癌の発症・進展である。単球由来線維細胞は骨髄由来免疫抑制細胞やM2マクロファージなどの免疫を負に調節する細胞とともに癌発症・進展に関与すると考えられている。がん治療の場では免疫チェックポイント阻害剤による細胞傷害性T細胞の抗腫瘍効果増強が注目されているが、我々はケモカイン(CCL2とCX3CL1)による単球の炎症部位への動員とマクロファージ・線維細胞への分化を制御することが大腸炎関連線維化および大腸癌の発症を抑制することを明らかにした。このことは炎症性腸疾患患者の大腸癌発症予防法開発に繋がると期待される。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS.2017
Author(s)
Tawara I, Kageyama S, Miyahara Y, Fujiwara H, Nishida T, Akatsuka Y, Ikeda H, Tanimoto K, Terakura S, Murata M, Inaguma Y, Masuya M, Inoue N, Kidokoro T, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Naoe T, Emi N, Yasukawa M, Katayama N, Shiku H.
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Journal Title
Blood
Volume: 130
Issue: 18
Pages: 1985-1994
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CXCL12-CXCR4 axis is required for contact-mediated human B lymphoid and plasmacytoid dendritic cell differentiation but not T lymphoid generation.2017
Author(s)
Minami H, Nagaharu K, Nakamori Y, Ohishi K, Shimojo N, Kageyama Y, Matsumoto T, Sugimoto Y, Tawara I, Masuya M, Miwa H, Katayama N.
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Journal Title
J Immunol.
Volume: 199
Issue: 7
Pages: 2343-2355
DOI
Related Report
Peer Reviewed
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[Journal Article] Attempt to Harvest a Sufficient Number of Mononuclear Cells in an Appropriate Blood Product Volume By Modification of the Default Apheresis Setting.2017
Author(s)
Tanaka Y, Ohishi K, Sawai T, Iwasaki H, Kageyama S, Masuya M, Matsumoto T, Tanigawa T, Wada H, Shiku H, Ito M, Katayama N
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Journal Title
Ther Apher Dial.
Volume: 21
Issue: 5
Pages: 507-511
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Management of Pulmonary Mucormycosis Based on a Polymerase Chain Reaction (PCR) Diagnosis in Patients with Hematologic Malignancies: A Report of Four Cases2017
Author(s)
Ino K, Nakase K, Nakamura A, Nakamori Y, Sugawara Y, Miyazaki K, Monma F, Fujieda A, Sugimoto Y, Ohishi K, Masuya M, Katayama N.
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Journal Title
Internal Medicine
Volume: 56
Issue: 6
Pages: 707-711
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed
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[Journal Article] irculating fibrocytes correlate with the asthma control test score.2016
Author(s)
Kobayashi H, Naito M, Masuya M, Maruyama M, Urata K, Takahashi Y, Tomaru A,Fujiwara K, Ohnishi M, Takagi T, Kobayashi T,D'Alessandro-Gabazza C, Urawa M,Gabazza EC, Taguchi O, Takei Y.
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Journal Title
Allergol Immunopathol (Madr).
Volume: 44
Issue: 3
Pages: 152-154
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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