| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We examined immunohistochemically the involvement of TNF α-mediated and mitochondria-mediated apoptotic pathway in pathogenesis of Sjogren's syndrome using autoimmune model mouse, MRL/lpr mice, and control mice, MRL/+ mice, in our present study. 5-month-old mice of each strain were sacrificed by anesthesia overdose followed by exsanguinations. Submandibular glands were removed, fixed in 10% buffered formalin, and embedded in paraffin. Paraffin-embedded tissue sections (3μm) were immunostained against TNF α, TNF receptor 1, Fadd, caspase 8, caspase 3, which are implicated in TNF α-mediated apoptotic pathway, in addition to caspase 2, Bid, p53, PUMA Bax, cytochrome c, Apsf-1, caspase 9, which are related to mitochondria-mediated apoptosis, using streptoavidin-biotin method. The specimens of MRL/lpr mice showed intense expression of these ligands in ductal cells of submandibular glands. However, the immunolocalizations of these ligands in MRL/+ mice were weak and not convincing.
It has been revealed that tissue destruction of salivary glands observed in Sjogren's syndrome is triggered by apoptosis, and Fas-Fas ligand apoptotic pathway plays a crucial role in the pathogenesis of this disease. We have also confirmed that, impaired submandibular gland tissues of MRI/lpr mice attribute to the commitment to apoptosis through ssDNA expression. Furthermore, Fas-Fas ligand apoptotic pathway is abrogated in MRL/lpr mice because they carry a mutant of fans gene. Therefore, our present, study indicates that TNF α-mediated and mitochondria-mediated apoptotic pathway other than Fas-Fas ligand apoptotic pathway has the association with the development, of Sjogren's syndrome-like sialadenitis in MRL/lpr mice.
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