2007 Fiscal Year Final Research Report Summary
Study on Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis
| Project/Area Number |
17591061
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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 | National Institute of Infectious Diseases |
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Principal Investigator |
SATOSHI Yamagoe National Institute of Infectious Diseases, Bioactive Molecules, Senior Researcher (00212283)
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| Co-Investigator(Kenkyū-buntansha) |
大川原 明子 国立感染症研究所, 生物活性物質部, 主任研究官 (30260277)
YAMAGOE Satoshi National Institute of Infectious Diseases, Bioactive Molecules, Senior Researcher (00212283)
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| Project Period (FY) |
2005 – 2007
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| Keywords | molecules on a living body / physiological activity / immunology / pathology / Medical treatment and welfare |
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| Research Abstract |
Objective. We previously reported that the Va15811e polymorphism of the human leukocyte cell-derived chemotaxin 2 (LECT2) gene is associated with severity of rheumatoid arthritis (RA). To define the role of LECT2 in inflammatory arthritides, we investigated the development of collagen antibody-induced arthritis (CAIA) in LECT2-deficient (LECT24^-/-) mice.
Methods. CAIA was induced in mice by administering anti-type II collagen antibodies followed by lipopolysaccharide. Daily assessment of hind paw swelling was used to monitor the development of arthritis. Histopathological features and expression of inflammatory cytokines were also analyzed. We confirmed the role of LECT2 by introducing a LECT2 expression-vector into LECT2^-/- mice by a hydrodynamic gene transfer method.
Results. Arthritis in LECT2^<-/-> mice was significantly exacerbated compared to wild-type controls. Histopathology of the tarsal joints showed that inflammation and the erosion of cartilage and bone in LECT2^<-/-> mice was more severe than in controls. Interleukin-16, interleukin-6 and certain chemokines were present at significantly higher levels in the arthritic hind paws of LECT2^<-/-> mice. On the other hand, the amount of LECT2 in the serum and locally in the hind paw was higher in arthritic wild-type mice. Finally, hydrodynamic gene transfer experiments revealed that the severity of arthritis was reduced by the systemic expression of exogenous mouse LECT2 protein in LECT2^<-/-> mice.
Conclusion. These results strongly suggest that LECT2 directly suppresses the development of CAIA. Manipulation of LECT2 might provide a rationale for novel therapeutic approaches to the treatment of inflammatory arthritides, such as RA.
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[Journal Article] Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis.2008
Author(s)
Okumura, A., Saito, T., Otani, I., Kojima, K., Y., Ishida-Okawara, A., Nakazato, K., Asano, M., Kanayama, K., Iwakura, Y., Suzuki, K., Yamagoe, S.
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Journal Title
Arthritis, Rheumatism 58
Pages: 413-421
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of leukocyte cell-derived chemotaxin 2 in the toxic shockcaused by staphylococal enterotoxin A2008
Author(s)
Kato, H., Minh, DH., Yamagoe, S., Suzuki, K., Ueshiba, H., Imanishi, K, Uchiyama, T., Yagi, J.
Organizer
The 81th Annual Meeting of the Japanese Society for Bacteriology
Place of Presentation
Kyoto
Year and Date
20080324-26
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of leukocyte cell-derived chemotaxin 2 in the toxic shockcaused by staphylococal enterotoxin A2007
Author(s)
Minh, DH., Kato, H., Ueshiba, H., Imanishi, K., Suzuki, K., Yamageoe, S., Uchiyama, T., Yagi, J.
Organizer
The 37th Annual Meeting of the Japanese Society for Immunology
Place of Presentation
TOKYO
Year and Date
20071120-22
Description
「研究成果報告書概要(欧文)」より
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