Willems F, Amraoui Z, Vanderheyde N, Verhasselt V, Aksoy E, Scaffidi C, Peter M E, Krammer P H, Goldman M
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Brussels, Belgium.
Blood. 2000 Jun 1;95(11):3478-82.
To gain insight into the mechanisms controlling apoptosis of dendritic cells (DC), human monocyte-derived DC were analyzed for their expression of CD95 (Fas/Apo-1) and their response to CD95 ligation. Although DC expressed the CD95 molecule on their membrane, they did not undergo apoptosis on CD95 ligation unless sensitized by cycloheximide. In parallel, DC synthesized c-FLIP(L), an inhibitor of the CD95-mediated death-signaling cascade. We also demonstrated that bisindolylmaleimide down-regulates c-FLIP(L) expression in DC and, in parallel, allows CD95-mediated apoptosis in these cells. In contrast, Bcl-2, Bcl-x(L), and Bax levels were not affected by bisindolylmaleimide. We conclude that DC resist CD95- mediated apoptosis in association with c-FLIP(L) expression and that the immunosuppressive potential of bisindolylmaleimide previously observed at the T-cell level also involves facilitation of CD95-mediated DC apoptosis.
为深入了解控制树突状细胞（DC）凋亡的机制，对人单核细胞衍生的DC进行了分析，检测其CD95（Fas/Apo-1）的表达及其对CD95连接的反应。尽管DC在其细胞膜上表达CD95分子，但除非用放线菌酮致敏，否则它们在CD95连接时不会发生凋亡。同时，DC合成了c-FLIP(L)，一种CD95介导的死亡信号级联反应的抑制剂。我们还证明双吲哚马来酰胺可下调DC中c-FLIP(L)的表达，同时使这些细胞发生CD95介导的凋亡。相比之下，双吲哚马来酰胺对Bcl-2、Bcl-x(L)和Bax的水平没有影响。我们得出结论，DC与c-FLIP(L)的表达相关，抵抗CD95介导的凋亡，并且先前在T细胞水平观察到的双吲哚马来酰胺的免疫抑制潜力也涉及促进CD95介导的DC凋亡。
