- 學位論文
實驗性自體免疫前葡萄膜炎中Lymphotactin及其受體的表現
Expressions of Lymphotactin and Its Receptor, XCR, in Lewis Rats with Experimental Autoimmune Anterior Uveitis
摘要
急性前葡萄膜炎是人類最常見的葡萄膜炎型式。此眼疾會明顯導致視力障礙而且其確切的致病機制尚未有定論。本研究在實驗性自體免疫前葡萄膜炎的分子醫學機制研究中，成功地建立了路易斯大鼠的活體動物模式。因而在此實驗中，我們探究了實驗性自體免疫前葡萄膜炎中能將特定白血球分群細胞吸引到眼部發炎部位的一種趨化激素 lymphotactin 及其受體的表現。我們觀察到前房水中白血球的數量隨著虹膜與睫狀體的發炎狀態惡化而增加而且因 lymphotactin 及其受體於疾病進程的虹膜與睫狀體中即有此趨化激素基因核酸序列的相關表現；因而在其前房水中lymphotactin 蛋白質表現量亦於發炎狀態較高峯時有較高濃度產生。此外；本研究亦證實核轉錄因子抑制劑 PDTC ( Pyrrolidine dithiocarbamate, a nuclear factor kappa B inhibitor ) 可於發炎狀態較高峯時顯著抑制前房水中lymphotactin 蛋白質表現量。進而我們探究了流式細胞儀的分析結果顯示具有 lymphotactin 抗體呈色的CD8 + 毒殺型Ｔ細胞數量亦隨著發炎狀態惡化而增加；而且免疫組織化學染色法也呈現出 lymphotactin 表現於虹膜與睫狀體中浸潤的炎症細胞。總而言之，毒殺型Ｔ細胞所產生的 lymphotactin 是實驗性自體免疫前葡萄膜炎致病機制的重要角色而且參與疾病進程的發炎狀態中特定炎症細胞進入到虹膜與睫狀體的徵集。因此實驗性自體免疫前葡萄膜炎的虹膜與睫狀體之趨化激素 lymphotactin 及其受體的調節研究分析應有助於呈現疾病進程的機制進而期望能發展有效的生化檢驗方法並對阻斷此致病機制來緩解與治療人類的急性前葡萄膜炎的目標有所貢獻。
並列摘要
Acute anterior uveitis (AAU) is the most common form of uveitis in humans and the exact mechanism of AAU has yet to be determined. We have successfully created an animal model of Experimental Autoimmune Anterior Uveitis (EAAU) in Lewis rat. In this experiment, we studied the expression of lymphotactin – a chemokine which attracts lymphocytes to inflammation sites in the EAAU. We observed that the leukocytes of aqueous humor increased with the severity of inflammation of iris/ciliary body. There were specific lymphotactin and its receptor messenger RNA expressions in iris/cilicary body in EAAU. The expression of lymphotactin receptor in iris/ciliary body correlated with that of lymphotactin. Furthermore, the lymphotactin protein levels of aqueous humor also correlated with the disease process. Pyrrolidine dithiocarbamate (PDTC), a nuclear factor kappa B inhibitor, markedly inhibited the expression of lymphotactin protein in the aqueous humor. Immunohistochemical staining revealed that lymphotactin was expressed on infiltrated inflammatory cells of iris/ciliary body. Flow cytometry analysis revealed that there was increasing number of CD8 + cytotoxic T cells with positive lymphotactin staining with the severity degree of inflammation. In conclusion, lymphotactin played an important role in the pathogenesis of EAAU and could attract more inflammatory cells to the iris/ciliary body.