2004 Fiscal Year Final Research Report Summary
INVOLVEMENT OF APOPTOTIC PATHWAY IN PATHOGENESIS OF SJOGRENS SYNDROME
| Project/Area Number |
14571935
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
矯正・小児・社会系歯学
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
SAITO Keiichi TOHOKU UNIVERSITY, GRADUATE SCHOOL OF DENTISTRY, LECTURER, 大学院・歯学研究科, 助手 (00178477)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MORI Shiro TOHOKU UNIVERSITY, HOSPITAL, ASSISTANT PROFFESSOR, 病院・講師 (80230069)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | SJOGREN'S SYNDROME / APOPTOSIS / MITOCHONDRIA / TNF ALPHA / IMMUNOHISTOCHEMISTRY |
|---|
| 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.
|
