2007 Fiscal Year Final Research Report Summary
Crosstalk between inflammation and adhesion
| Project/Area Number |
18591079
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NAKAMOTO Tetsuya Tokyo Medical and Dental University, Department of Rheumatology, COE member (90334383)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Takayuki Osaka City Universit, Department of Physiology, Assistant Professor (50343413)
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| Project Period (FY) |
2006 – 2007
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| Keywords | immunology / Signal Transduction / inflammatory cells / cell adhesion |
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| Research Abstract |
We investigated how proteins of integrin signaling pathway are involved in inflammation.
Cas-L/Hef1/Nedd9 is a member of p 130cas family proteins that are involved in integrin signaling. Although the roles of Cas-L in lymphocytes are reported, its expression in granulocytes was not known. We first showed the expression of Cas-L protein in neutrophils. Tyrosine phosphorylation of Cas-L was observed with the stimulation by LPS, TNF, or fMLP. The tyrosine phosphorylation was enhanced with the adhesion of neutrophils. Granulocytes from Cas-L deficient mice showed enhanced migration in response to fMLP.
CIZ is a nucleo-cytoplasmic shuttling protein that binds to p 130Cas and transcriptionally regulates collagens and matrix metalloproteinases. We screened for new binding partners of CIZ. CIZ binds to the C-terminal domain of collagens in the nucleus, suggesting the transcriptional regulation of collagens by this complex.
We applied the serum-induced arthritis model to CIZ-deficient mice. CIZ deficiency reduced arthritis severity to half of that in wild-type mice. CIZ deficiency reduced inflammatory cell invasion and cartilage destruction. CIZ deficiency suppressed the arthritis-induced increase in the number of osteoclasts in the joint, urinary deoxypyridinoline, and mRNA expression of RANKL. Arthritis-induced increase of mRNA expression of MMP-3, a target of CIZ as a transcription factor, was decreased by CIZ deficiency together with the mRNA expression of Adamts4, IL-1β, and CXCL16. These results suggest that CIZ plays pivotal roles in the induction of inflammatory genes.
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[Journal Article] Functional analysis Src homology 3-encoding exon (exon2) of pl30Cas in primary fibroblasts derived from exon 2-specific knockout mice.2008
Author(s)
Tazaki, T., Miyazaki, K., Hiyama, E., Nakamoto. T., Sakai, R., Yamazaki, N., Honda, Z. I., Noda, M., Miyasaka, N., Sueda, T., Honda, H.
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Journal Title
Genes to Cells 13
Pages: 145-157
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression and tyrosine phosphorylation of Crk associated substrate lymphocyte type (Cas-L) protein in human neutrophils.2008
Author(s)
Nakamoto. T., Seo, S., Sakai, R., Kato, T., Kutsuna, H., Kurokawa, M., Noda, M., Miyasaka, N., Kitagawa, S.
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Journal Title
J Cell Biochem 105(1)
Pages: 121-128
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Deficiency of CIZ suppresses serum-induced arthritis.2008
Author(s)
T. Nakamoto, Mizoguchi, Y. Izu, T. Hayata, Y. Ezura, D. Mathis, C. Benoist, N. Miyasaka, M. Noda
Organizer
ASCB 47th Annual Meeting
Place of Presentation
Washington, DC, USA
Year and Date
2008-12-01
Description
「研究成果報告書概要(欧文)」より
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