| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Purpose : Development of organ-specific autoimmune diseases, including uveitis, is thought to be regulated by signals transmitted between local tissue-specific cells and circulating immune cells. In this study, we attempted to identify chemoattractive signals specific for the development of uveitis in behcet's disease (BD) by by comparing total gene expression in experimental autoimmune uveoretinitis (EAU).
Methods : C57BL/6 mice were immunized with 200 mg of BSA, peptide 35-55 of myelin oligodendrocyte protein (MOG-p), or hIRBP-p emulsified in complete Freund's adjuvant. On day 14, retinas and splenic T cells were collected, and total RNAs were extracted. The expression profiles of approximately 20,000 potentially relevant genes were analyzed using pooled RNA samples within individual groups and the Codelink Bioarray system. The data were evaluated by the gene expression ratio of each experimental group versus non-immunized control group. In addition, CXCL7 mRNA expression was analyzed
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in periphral monocytes in 15 BD patients by real time PCR.
Results : In the retina of mice immunized with hIRBP-p that induce EAU, genes of CCL5, CXCL9, and CXCL10 related to Th1 cell recruitment and those of CCL7, CCL8 and CCL17 associated with Th2 cell recruitment were preferentially expressed compared with other chemokine genes. Although these chemokine genes were also expressed in the retina of mice immunized with MOG-p that induce optic neuritis in addition to experimental autoimmune encephalomyelitis, the overall level of expression was lower than that in the retina with induced EAU. In T cells, EAU-specific Th1 or Th2 chemokine gene expression was not observed. Interestingly, gene of CCL2, CCL24 or CXCL7 responsible for macrophage and neutrophil recruitment was specifically detected in the retina and T cells of mice with induced EAU and not in the other immunized groups. CXCL7 mRNA expression was increased in BD with active uveitis compared with BD with uveitis on remission or healthy contro Less
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