三氧化二砷對樹突細胞之影響

Effect Of Arsenic trioxide On Monocyte Derived Dendritic Cells

趙素嬌(Shu-Chauo Chou)

指導教授 ： 劉柯俊 博士 ； 高淑慧 博士

臺北醫學大學/醫學院/醫學檢驗生物技術學研究所/碩士(2004年)

摘要

三氧化二砷目前用於治療前骨髓性白血病，會造成癌細胞凋亡，而達到治療之效果。在我們的研究顯示由單核球誘導樹突細胞產生過程中加入三氧化二砷，會抑制c-Rel、NF-κBp50 表現，進而調控樹突細胞的訊息傳遞，降低樹突細胞CD86之表現、降低樹突細胞IL-12p70、IL-1β、IL-10之分泌量、降低刺激異體淋巴球增殖之能力、降低刺激異體naïve T 細胞細胞內IFN-γ表現量及降低樹突細胞引起Th1/Th2之能力。根據此結果顯示三氧化二砷會在體外影響由單核球誘導產生之樹突細胞的功能，可能因此降低體內免疫功能。

關鍵字

三氧化二砷 ； 樹突細胞

並列摘要

Arsenic trioxide (As2O3) has been applied to treat acute promyelocytic leukemia (APL) recently according to its proapototic effect on APL cells. In our study, we can observed that, during differentiation of monocyte into DCs in vitro, As2O3 suppressed c-REL, NFκBp50 expression and regulated signal transduction process in DCs. Adding arsenic trioxide down- regulated CD86 expression and decreased IL-12p70, IL-1β, IL-10 secretion, decrease the allogeneic lymphocyte stimulation capacity of DCs, The intracellular IFN-γ expression of T cells stimulated with As2O3 treated DCs, and the capacity of these DCs to promote Th1/Th2 activation were reduced. According to our results, arsenic trioxide may suppress immunologic response via influence on the function of monocyte derived DCs.

並列關鍵字

Arsenic trioxide ； Dendritic Cells

參考文獻

Banchereau, J. and Steinman, RM. (1998) Dendritic cells and the control of immunity. Nature, 392, 245-252.

Boffa, D., Feng, B., Sharma, V., Dematteo, R., Suthanthiran, M., Nunez, R., Liou, HC. (2003) Selective loss of c-Rel compromise dendritic cell activation of T lymphocytes. Cell immunol., 105-115

Borkowski, TA., Letterio, JJ., Farr, AG. and Udey, MC. (1996) A role for endogenous transforming growth factor β1 in Langerhans cell biology: the skin of transforming growth factor β1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med., 184, 2417-2422.

Brocker, T. (1997) Survival of mature CD4 T lymphocytes is dependent on MHC class II expressing dendritic cells. J. Exp. Med., 186, 1223-1232.

Chen, YC., Lin-Shiau, SY., Lin, JK. (1998) Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J. Cell. Physiol., 177, 324-333.