| Project/Area Number |
17K16177
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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 |
Hematology
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| Research Institution | Akita University |
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Principal Investigator |
YONGMEI GUO 秋田大学, 医学部附属病院, 助教 (20617386)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 造血制御 / LPS / TLR4 / CD34＋造血幹細胞 / 好中球 / CD34＋細胞 / 顆粒球 / 造血 / パターン認識受容体 / 情報伝達経路 / 細胞膜型PRRｓ / 細胞質型PRRｓ |
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| Outline of Final Research Achievements |
In our research, we demonstrated that lipopolysaccharide (LPS), a cell wall outer membrane component of Gram-negative bacteria, promoted neutrophil/monocytic hematopoiesis via Toll like receptor 4 (TLR4) expressed on hematopoietic stem cells. The production of interleukin-6 (IL-6) was increased through activating of TLR4 signal pathway and the expression of neutrophil transcription factor C/EBPβ and monocyte transcription factor PU.1 increased. Neutrophil/monocytic hematopoiesis was promoted by enhanced expression of C/EBPβ and PU.1.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトCD34+造血幹細胞を用いて、in vitroで病原微生物由来物質による造血幹細胞の分化増殖制御機構の存在を確認できた。IL-6は定常状態及び応急状態のいずれにおいても好中球造血に関与していること、C/EBPβは感染時に造血幹細胞や前駆細胞の増幅に関与していることがマウスの系で観察され、我々の研究から、ヒトCD34+造血幹細胞においても確認できた。
細菌感染時、応急的な好中球増加や左方移動等、臨床的な常識を分子的機序で説明できた。
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