| Project/Area Number |
16590992
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
KAWAHITO Yutaka Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 講師 (50336731)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Toshikazu Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (90158410)
TOKUNAGA Daisaku Kyoto Prefectural University of Medicine, School of Medicine, Associate professor, 医学部, 准教授 (90343409)
NAKADA Hiroshi Kyoto Sangyo University, Department of Biotechnology, Faculty of Engineering, Professor, 工学部, 教授 (90113141)
SANO Hajime Hyogo college of medicine, School of Medicine, Professor, 医学部, 教授 (00196304)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | mucin inducing COX-2 / rheumatoid arthritis / abnormality of carbohydrate chain / COX-2 / ムチン |
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| Research Abstract |
Purpose
Abnormality of carbohydrate chain of mucin, which is enriched in synovial fluid (SF), has a possibility to relate with pathological conditions of rheumatoid arthritis (RA) such as the production of IL-1, TNF-a and PGE 2 in joints. In this study, we examine to detect a new mucin as a therapeutic target of RA and analyze its biological activity and structure.
Results
1) Immunohistochemical analysis showed that superficial synovial cells, and infiltrating inflammatory mononuclear cells in RA synovial tissues express MUC-1, Tn and sialyl Tn which are typical malignancy-associated mucins.
2) Western blot analysis revealed that SF faractions purified by gel filtration and further purified preparation by desalination and density-gradient centrifugation include MUC-1, Tn and sialyl Tn.
3) The newly discovered mucin from SF in patients with RA can stimulate the production of IL-1, TNF-a and PGE2 in human peripheral blood monocytes (PBMC).
Perspective
We revealed that MUC-1, Tn and sialyl Tn expressed in synovial tissues. We also found a new mucin purified from SF in patients with RA, which can produce cytokines and PGE2 on PBMC. This mucin may be mainly MUC-1. We are going to analyze its structure as a therapeutic target of RA and also examine the pathological mechanism including the proliferation of synovial cells and the induction of osteoclast.
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