2002 Fiscal Year Final Research Report Summary
Role of Chemokines in the Pathogenesis of Bleomycin-induced Scleroderma
| Project/Area Number |
12670810
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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 |
Dermatology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YAMAMOTO Toshiyuki Lecturer,Department of Dermatology,Tokyo Medical and Dental Univesity, 医学部附属病院, 講師 (30242192)
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| Project Period (FY) |
2000 – 2002
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| Keywords | scleroderma / chemokine / MCP-1 / Bleomycin |
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| Research Abstract |
Recent findings suggest the involvement of chemokines in the fibrotic process. We reported that MCP-1 upregulates mRNA expression of not only collagen, but also collagenase and tissue inhibitor of metalloproteinase-1 (TIMP-1) (J Immunol 2000; 164: 6174-6179). MCP-1 was strongly detected in the lesional skin of systemic sclerosis (SSc) (J Dermatol Sci 2001; 26: 133-139), and spontaneous mRNA expression of MCP-1 was also elevated in scleroderma fibroblasts (Eur J Immunol 2001; 31: 2936-2941). We previously established a mouse model for scleroderma by repeated injections of bleomycin, mimicking human scleroderma both histologically and biochemically (J Invest Dermatol 1999; 112: 456-462, J Rheumatol 1999; 26: 2628-2634, Arch Dermatol Res 2000; 292: 535-541). In this model, expression of MCP-1 as well as its receptor, CCR-2, was enhanced in the lesional skin following bleomycin treatment, in vivo neutralization with anti-MCP-1 antibody together with local bleomycin treatment reduced the development of dermal sclerosis. In vitro data demonstrated that MCP-1 upregulates mRNA expression of extracellular matrix proteins. These data suggest MCP-1/CCR-2 pathway plays an important role in the pathogenesis of bleomycin-induced scleroderma.
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