https://scholars.lib.ntu.edu.tw/handle/123456789/163792
標題: | 行政院國家科學委員會專題研究計畫成果報告:檳榔成分對T淋巴球細胞激素基因表現之作用與機轉研究 | 作者: | 詹東榮 | 關鍵字: | areca quid;immune;T cell activation;cytokine | 公開日期: | 2004 | 出版社: | 臺北市:國立臺灣大學獸醫學系暨研究所 | 摘要: | 流行病學研究顯示嚼食檳榔是罹患口腔鱗狀上皮細胞癌的危險因子,實驗證據指出口 腔鱗狀上皮細胞癌的致病原因和病人免疫機能的惡化密切相關。本研究的主要目的即在研 究檳榔成分對T 細胞增生、活化和細胞激素基因表現的影響並探討其可能的作用機制,小 鼠脾臟細胞先加入檳榔萃取物(ANE)、檳榔鹼、arecaidine 或黃樟素處理,再以PMA/Io 或 CD3 合併CD28 單株抗體(CD3/CD28)刺激。ANE 處理顯著的抑制脾臟細胞的代謝活性以及 IL-2 和IFN-γ的分泌,但對IL-4 則只有輕微的抑制效果。檳榔鹼、arecaidine 或黃樟素(1-100 µM)的處理對脾臟細胞分泌細胞激素並無影響。ANE 對CD3/CD28 刺激所誘發的脾臟細胞 表現細胞激素IL-2 和IFN-γ的mRNA 也具有顯著抑制作用,這項作用和上述ANE 抑制細 胞激素分泌的結果相吻合。除了脾臟細胞,ANE 對EL4 細胞的活化和細胞激素的分泌也呈 現出類似的抑制作用,ANE 並會導致EL4 細胞出現DNA laddering 的現象,顯示細胞受到 ANE 的作用而發生細胞凋亡的現象。綜合上述結果,本研究顯示ANE 對T 細胞的增生和 Th1 細胞激素的表現具有顯著的抑制作用,這個作用並非是檳榔鹼或arecaidine 所造成,實 驗證據也顯示ANE 抑制細胞激素製造的可能機轉之一是經由誘發T 細胞發生細胞凋亡。 Betel quid chewing is a risk factor for oral squamous cell carcinoma (SCC). Experimental evidence suggests that the pathogenesis of SCC is associated with immune deterioration. The objective of the present studies was to investigate the effect of areca nut extract (ANE) on T-cell proliferation, activation and cytokine expression, and its underlying mechanisms. Murine splenocytes were pretreated with ANE, arecoline, arecaidine or safrole followed by stimulation with phorbol-12-myristate-13-acetate plus ionomycin (PMA/Io) or anti-CD3 plus anti-CD28 monoclonal antibodies (CD3/CD28). ANE pretreatment markedly attenuated both the cell metabolic activity, and the production of interleukin (IL)-2 and interferon (IFN)-γ. In contrast, ANE pretreatment only slightly inhibited IL-4 secretion. Pretreatment of cells with arecoline, arecaidine, or safrole (1-100 µM) did not affect the cytokine production. Consistent with the effect on cytokine production, ANE pretreatment markedly suppressed the steady state mRNA expression of IL-2 and IFN-γ by CD3/CD28-stimulated splenocytes. The inhibitory effects of ANE on splenocyte activation and cytokine production were also demonstrated in EL4 cells. Furthermore, ANE treatment induced the formation of DNA ladder in EL4 cells, indicating apoptosis of cells in the presence of ANE. Collectively, the present studies demonstrated that Th1 cytokine expression by T cells was attenuated by ANE pretreatment, which was apparently not mediated by arecoline and arecaidine. The results also suggest that the suppression of cytokine production by ANE is, at least in part, mediated by induction of T-cell apoptosis. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/28731 | 其他識別: | 922320B002093 | Rights: | 國立臺灣大學獸醫學系暨研究所 |
顯示於: | 獸醫學系 |
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