Graninger W B, Steiner C W, Graninger M T, Aringer M, Smolen J S
Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Austria.
Cell Death Differ. 2000 Oct;7(10):966-72. doi: 10.1038/sj.cdd.4400724.
Both faulty regulation of apoptosis and the inappropriate expression of several interleukins have been considered important defects of lymphocytes in the human autoimmune disease systemic lupus erythematosus (SLE). We therefore tested the in vitro effect of recombinant interleukin (IL-)-2, 4, 7, and 15 on peripheral blood mononuclear cells from patients with SLE and from healthy volunteers. Intracellular Bcl-2 and Bax expression was measured by fluorocytometry and the rate of apoptosis was determined by the TUNEL technique and propidium iodide staining. IL-2, IL-4, IL-7 and IL-15 led to a significant increase in Bcl-2 and a reduction in cell death rates, which was even more pronounced in SLE. Bax levels remained unchanged. Interestingly, the high ex vivo Bcl-2 content of lymphocytes from some SLE patients was maintained after growth factor withdrawal. Anti-apoptotic cytokine signaling may significantly influence the deregulation of cell death in SLE lymphocytes.
细胞凋亡调控异常和多种白细胞介素表达不当都被认为是人类自身免疫性疾病系统性红斑狼疮（SLE）中淋巴细胞的重要缺陷。因此，我们测试了重组白细胞介素（IL）-2、4、7和15对SLE患者和健康志愿者外周血单个核细胞的体外作用。通过荧光细胞术检测细胞内Bcl-2和Bax的表达，并通过TUNEL技术和碘化丙啶染色确定细胞凋亡率。IL-2、IL-4、IL-7和IL-15导致Bcl-2显著增加，细胞死亡率降低，这在SLE中更为明显。Bax水平保持不变。有趣的是，在撤出生长因子后，一些SLE患者淋巴细胞的高离体Bcl-2含量得以维持。抗凋亡细胞因子信号可能显著影响SLE淋巴细胞中细胞死亡的失调。
