1994 Fiscal Year Final Research Report Summary
Induction of differentiation of human myelogenous leukemic cells and signal transduction
| Project/Area Number |
04671369
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
TAKEDA Ken Shouwa Universiy Associate School of Medicine Professor, 医学部, 助教授 (80054013)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Sanju Showa University Assistant Scool of Medicine, 医学部, 助手 (50176567)
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| Project Period (FY) |
1992 – 1994
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| Keywords | myeloid leukemia / differentiation / TNF / TNF receptor / signal transduction / ADP-ribosylation / ML-1 / macrophage |
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| Research Abstract |
Human myelogenous leukemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors. We have succeeded in purifing one of these factors from leukocyte conditioned medium and identified it as TNF.TNF interacts with target cells by binding to two receptors, 55 kDa and 75 kDa. We examined the functions of these two TNF receptors in induction of differentiation of ML-1 cells. Differentiation was monitored by assessing the appearance and accrual of various cellular markers that are usually associated with maturation of the monocytic elements. 1) The ratio of 55 kDa/75 kDa TNF receptors of ML-1 cells was 1/4.2) Bothe TNF receptors were involved in induction of differentiation of ML-1 cells. Stimulation of either receptor type alone could induce differentiation, but simultaneous stimulation of both receptors induced it more effectively.
We also clarified that TNF synergistically induced differentiation of ML-1 cells in combination with certain bacterial toxins such as choleratoxin and enterotoxin. They acted via ADP-ribosylation of GTP-binding proteins that were coupled to certain effectors other than adenylate cyclase.
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