| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Research Abstract |
Sjogren's syndrome (SS) is, an organ-specific automimmune disease, caused by the progressive loss of exocrine glands and is associated with several autoimmune phenomena. Several reports have suggested that viral infection could be these environmental agents in SS.Evidence for an association between Epstein-Barr virus (EBV) infection and SS has been accumulating. EBV antigens and increased levels of EBV DNA have been found in infiltrating lymphocytes and salivary gland epithelial cells of SS ptients. Infections EBV is present in both the saliva of SS patients and culture supernatants of cell lines established from SS patients. These reports suggest that a reactivated EBV infection may play a role in SS,contributing to the initiation or perpetuation of an immune response in the target organs. However, pathological roles of the virus, if any, remain obscure. To understand the precise mechanism of EBV reactivation, we developed in vitro model for salivary gland cells using ZP-CAT vector and evaluated the effect of known several cytokines such as IL-1, TNF,IL-6, EGF and IFN-gamma. The ZP-CAT transfected human salivary gland cell line, HSG were assayd for CAT expression after treatment with several cytokines and saliva from SS patients. To detect the transcritional pathway for ZP activation, immunoblots of tyrosine kinase, MAP kinase and JAK-STAT were also performed. ZP-CAT transfected HSG cells showed statistically significant increase in CAT activity following stimulation with TNF,IL-10, EGF,and saliva from SS patients. Normal healthy saliva did not show statistically significant increase. The tyrosine kinase phosphorylation was detected in these CAT-positive samples. The use of ZP-CAT transfected HSG cells appear to be an efficient and simple method to use to screen for cancidates for EBV reactivation.
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