| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
One of the tonsil-Mated disease, IgA nephropathy (IgAN), the most common form of primacy glomerulonephritis, is recognized as one of the tonsil-related diseases since the disease often gets worse after and/or during acute tonsillitis and the disease progression is often prevented by tonsillectomy. Although several reports showed an increase in IgA production of tonsillar mononuclear cells (TMC), its mechanism has not fully clarified yet. Recently, B-cell-activation factor (BAFF), which stimulates B-cell proliferation and immunoglobulin production, was identified. Unmethylated deoxycytidyl-deoxyguanosine oligodeoxynucleotide (CpG-ODN), which is able to mimic the immunostimulatory activity of microbial DNA, is known to be involved in the production of immunoglobulins and some cytokines. In this study, we focused on roles of BAFF and IFN-γ in IgA production of TMC stimulated with CpG-ODN in IgAN patients. Two-color flow cytometric analysis revealed that the intercellular expression of IFN-γ on the T-cells fleshly isolated from tonsils showed significantly higher in IgAN patients than in non-IgAN patients. The spontaneous productions of IgA and IFN-γ of TMC were significantly higher in IgAN patients than in non-IgAN patients. Under stimulation with CpG-ODN, the productions of IgA, BAFF and IFN-γ of TMC were significantly higher in IgAN patients than in non-IgAN patients. The IgA production of TMC stimulated by CpG-ODN was inhibited by the treatment with anti-BAFF antibody and/or anti-IFN-γ antibody. Under stimulation with IFN-γ, the BAFF expression on the CD1c cells and the BAFF production of TMC were significantly higher in IgAN patients than in non-IgAN patients. These data suggest that hyper-immune response to microbial. DNA may be present in IgAN patients and may lead to hyperproduction of BAFF up-regulated by IFN-γ, resulting in hyperproduction of IgA in IgAN patients.
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