Project/Area Number |
22390179
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Kagoshima University |
Principal Investigator |
HASHIGUCHI Teruto 鹿児島大学, 大学院・医歯学総合研究科, 教授 (70250917)
|
Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Koichi 大阪工業大学, 工学部, 特任教授 (10381170)
MARUYAMA Ikuro 鹿児島大学, 大学院・医歯学総合研究科, 特任教授 (20082282)
ITO Takashi 鹿児島大学, 大学院・医歯学総合研究科, 特任講師 (20381171)
OYAMA Yoko 鹿児島大学, 医学部・歯学部付属病院, 特任助教 (20583470)
SHIMIZU Toshiaki 鹿児島大学, 大学院・医歯学総合研究科, 助教 (50468055)
|
Co-Investigator(Renkei-kenkyūsha) |
TAKENOUCHI Kazunori 鹿児島大学, 医学部・歯学部付属病院, 医員 (30646758)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
|
Keywords | 神経 / 免疫 / VEGF / リンパ節 / B細胞 / 高内皮小静脈 / LPS tolerance / B cell / immune / lymph / spleen / iron / HEV / angiogenesis / VEGF-A / POEMS syndrome / immune system / nervus system / lymph node / high endothelial venule / mouse |
Research Abstract |
Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recentstudies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19Cre/hVEGF-Afl) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses. 交付決定額
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