2002 Fiscal Year Final Research Report Summary
Curative effects of CpG DNA administration on scleroderma-like syndrome of Tsk/+mice
| Project/Area Number |
13670466
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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 |
内科学一般
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| Research Institution | Yokohama City University School of Medicine |
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Principal Investigator |
ICHINO Motohide Yokohama City University School of Medicine Department of Immunology and Parasitology, Assistant Professor, 医学部, 助手 (60271368)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAZAWA Masatoshi Yokohama City University School of Medicine Department of Immunology and Parasitology, Lecturer, 医学部, 講師 (20217699)
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| Project Period (FY) |
2001 – 2002
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| Keywords | CpG DNA / Scleroderma / Tsk / + mice / Th1 / Th2 / Autoimmune disease |
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| Research Abstract |
The tight-skin (Tsk/+) mice spontaneously develop scleroderma-like disease characterized by cutaneous hyperplasia, auto antibodies and pulmonary emphysema. IL-4, a typical Th2 cytokine, has been suggested to play an important role in the pathogenesis.
Here, we examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducer of Th1 cytokines, to prevent the development of scleroderma-like syndrome of Tdk/+mice. After 7 times administration of CpG ODN with 3-wk interval into 1-wk old Tsk/+ mice, dermal fibrosis was significantly reduced and low levels of serum antinuclear antibodies were detected. Furthermore, CpG ODN had a long-term inhibitory effect on the development of skin fibroses. IFN-γ producing cells induced by CpG ODN administration might contribute to inhibit the development of skin thickness.
However, no curative effect was observed on lung emphysema. The mechanisms of emphysema development could be independent of Th1/Th2 cytokine balance. When CpG ODN administration was started with 6-wk old Tsk/+ mice, the pathogenesis of the disease was not improved.
Theses results indicate that a Th1-biased cytokine milieu induced by CpG ODN ameliorate scleroderma-like syndrome, and support that CpG ODN treatment may be a feasible approach in the therapy of Th2-driven diseases.
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