2013 Fiscal Year Final Research Report
Endogenous TLR4 ligands in tumor metastasis.
| Project Area | Homeostatic inflammation: Molecular basis and dysregulation |
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| Project/Area Number |
21117008
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
MARU Yoshiro 東京女子医科大学, 医学部, 教授 (00251447)
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAMURA Sachie 東京女子医科大学, 医学部, 准教授 (60313087)
TSUKAHARA Fujiko 東京女子医科大学, 医学部, 講師 (40119996)
TOMITA Takeshi 東京女子医科大学, 医学部, 助教 (20302242)
DEGUCHI Atsuko 東京女子医科大学, 医学部, 助教 (10422932)
IEGUCHI Katsuaki 東京女子医科大学, 医学部, 助教 (90586348)
TAKITA Morichika 東京女子医科大学, 医学部, 助教 (80533455)
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| Project Period (FY) |
2009-07-23 – 2014-03-31
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| Keywords | TLR4 / SAA3 / S100A8 / CCL2 / ephrinA1 / 自然免疫 / がん転移 |
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| Research Abstract |
We focused on five points (1)endogenous ligands for TLR4 (2)homeostasis inflammation (3)pathological condition (4)translational research, and (5)generation of knockout mice. We showed conclusion as below.
(1)We showed binding between TLR4/MD-2 and peptide SAA3 (20-86). Binding site of S100A8 was center domain of TLR4. (2)Bronchial Clara cells contribute to lung metastasis by amplifying SAA3. (3)We found that C1D, a DNA-binding protein, is a novel endogenous ligand for TLR9. We found that TLR4 signaling plays a role in resistance to BCR-ABL kinase inhibitor, imatinib, in Chronic myeloid leukemia. (4)We identified mTOC as a Cerastramycin binding protein. We created human SAA3 ELISA system to quantitate SAA3 protein in culture media. We are investigating whether KB-R7785, an ADAM12 inhibitor, effect on lung metastasis by reduction of cleaved form of ephrin-A1. (5)To examine the homeostasis inflammation related to S100A8 and SAA3, we are trying to establish knockout mouse system.
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[Journal Article] Serum Amyroid A3 binds MD-2 to activates p38 and NF-kB pathway in a MyD88-dependent manner2013
Author(s)
Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y
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Journal Title
J Immunol. 2013
Volume: 191, 4, 2013
Pages: 1856-1864
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