| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
We hypothesized that IgA nephropathy (IgAN) is triggered by some exogenous antigen (s) which induces dysregulation of the mucosal immune system. To examine this mucosal immune system-orirnted hypothesis of IgAN,we have established a reproducible strain-nonspecific model of IgAN induced by oral administration of nivalenol (NIV) for 8 weeks.
In the present study, we further examined the effect of NIV administration fora longer periods, over 8 weeks, on the praogression of IgAN-like changes in glomeruli and immunoglobulin levels of mice. Long-term administration of NIV,significantly increased serum IgA levels as well as the intensity of glomerular IgA deposition in mice over time. Histopathological examination revealed more marked mesangial expansion in micegiven NIV for 12 months, though neither diffuseglobal sclerosis of glomeruli nor interstitial fibrosis suggesting sesrious renal injury were observed.
Moreover, some immunological studies were carried out to characterize mucosal T and AB
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cells isolated from mice with NIV-induced IgAN.Especially, our emphasis was focused on the effect of orally administered NIV on Peyer's patche(PP)T and B cells for their immunopathological contribution to the development of IgAN.As a result, a significant increase in IgA-producing cells was demonstrataed bay an enzyme-linked immunospot procedure in PP lymphocytes (PPL) of the NIV model mice. Upregulation of CD4^+ T cells was also revealed in PP of tahe model mice by a cytokine-specific reverse transcription-polymerase chain reaction which detected markedly high levels of mRNA specific for IL-4, IL-5, IL-6, IL-10 and TGF-beta as well as IFN-gamma and IL-2 (Th1 type cytokines)in these cells.
It was demonstrated that oral administration of NIV is obviously nephritogenic. IgAN-like changes in mice exacerbated over time in a period-dependent manner with NIV administration. It was suggested that PPL are ilmmunologically dysregulated in the NIV-induced IgAN,and that this kind of upregulation of the mucosalimmune system might be associated with the pathogenesis of IgAN.Taken together conclusively, the mucosal immune system-oriented hypothesis of IgAN seems to be reasonable. Less
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