| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
The pathogenesis of IgA nephropathy (IgAN) has never been elucidated. In the present study we created a novel reproducible IgAN model in mice which was orally induced by a mycotoxin, nivalenol (NIV), based on the hypothesis that IgAN is triggered by some exogenous antigen (s) which induces dysregulation of the mucosal immune system.
Significant IgA deposition in glomeruli and remarkable elevation of serum IgA levels were reproducibly induced in all C3H/HeN,C3H/HeJ and BALB/c mice fed NIV 12 ppm for 8 wk. When NIV in a low dose of 6 ppm for a long term of 6 to 12 months was administered to mice, the intensity of mesangial IgA deposition and the elevation of serum IgA levels gradually increased in the course of time. When we stopped NIV administration for 8 wk after we had given 12 ppm for 8 wk, less intense IgA deposition and lower serum IgA levels were observed in mice than they were in those fed 12 ppm just for 8 wk. Taken together, the NIV model is compatible with the mucosal immunity-oriented hypothesis above. Moreover, persistent NIV administration is important to induce and maintain the IgAN-like pathological changes.
A competitive ELISA using a deoxynivalenol-hemisuccinate-OVA conjugate revealed that serum IgA from the model mice has specifically high affinity to NIV.When spleen lymphocytes of the model mice were aseptically transferred to syngeneic control mice intraperitoneally, this adoptive transfer induced serum IgA elevated in the recipients. Therefore, it was confirmed that lymphocytes play a role in the induction of the IgAN model.
In conclusion, NIV reproducibly and strain-nonspecifically induces pathological changes in mice which resemble those in human IgAN ; the increased IgA is antigen-specific. We suggest that mycotoxins such as NIV are associated with the pathogenesis at least in some types of glomerulonephritis.
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