| Project/Area Number |
16591062
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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 |
Pediatrics
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| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
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Principal Investigator |
NAKAMURA Tsuneyuki Kanazawa medical university, Department of Pediatrics, assistant, 医学部, 助手 (40340004)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMURA Jun-ichi Kanazawa medical university, Department of Pediatrics, assistant, 医学部, 助手 (70367473)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | atypical mycobacteria / Kawasaki disease / model mouse / peroxiredoxin / angitis / coronary artery lesion / cytokine / endotherium |
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| Research Abstract |
The etiology of Kawasaki disease remains unknown. Induration of BOG vaccination site was frequently observed in this disease. This might result from superinfection with the related microbe(s) such as atypical mycobacteria. We have examined the immunopathology to a cross reactive antigen for coronary artery that might share the immunogenisity of a BOG component and atypical mycobacteria.The cell wall components of Microbacterium intracellulare (cwMI) were extracted. Female mice (C57BL/6J) of 3 week-old were inoculated subcutaneously with BCG or saline. Four weeks later, the animals were inoculated intraperitoneally with the cwMI or saline. The animals received BCG followed by cwMI developed coronary arteritis with infiltration of inflammatory cells (BCG+cwMI group). As controls, neither animals received saline followed by cwMI nor those received BOG followed by saline developed coronary arteritis. The animals in the BCG+cwMI group had significantly higher TNF-a and IFN-g production than the control groups (p<0.05). When multiple doses of cwMI were inoculated with BCG-inoculated mice, these cytokine production became more prominent By BLAST search, AhpC of MI had homology to peroxiredoxin of endothelium (35% identity). Intravenous injection with rabbit anti-peroxiredoxin serum also developed coronary arteritis and resulted in significantly higher TNF-a and IFN-g production than the control. These results indicated that molecular mimicry between BCG, atypical mycobacteria and endotherium components lead to the coronary arteritis in mice. Atypical mycobacteria superinfection in individuals who had BCG vaccination might develop coronary arteritis by cross reactive to peroxiredoxin as auto immune reaction. Our new model may clarify the etiology of Kawasaki disease.
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