Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Int J Cancer. 2013 Aug 1;133(3):766-70. doi: 10.1002/ijc.28067. Epub 2013 Mar 4.
Previously, interleukin (IL)-21 has been found to induce apoptosis by activating the signal transducer and activator of transcription 3 (STAT3) and concomitant upregulation of c-Myc in diffuse large B-cell lymphoma (DLBCL) lines with unknown Epstein-Barr virus (EBV) status. Here, as a first approach toward the characterization of the role of EBV in DLCBL, the EBV gene expression and the IL-21 sensitivity of the EBV-positive DLBCL line, Farage, have been examined. It was found that, surprisingly, despite c-Myc upregulation, IL-21 induced cell proliferation rather than apoptosis in Farage. Expression of a dominant-negative EBNA1 mutant and the consecutive downregulation of EBV gene expression antagonized the IL-21-induced proliferation of Farage and increased apoptosis. These findings reveal a previously unknown role of EBV in DLBCL that is of possible relevance for the current attempt to use IL-21 in therapy.
先前，白细胞介素 (IL)-21 通过激活信号转导和转录激活因子 3 (STAT3) 和随之而来的弥漫性大 B 细胞淋巴瘤 (DLBCL) 细胞中 c-Myc 的上调，被发现可诱导细胞凋亡，但 EBV 状态未知。在这里，作为对 EBV 在 DLCBL 中作用进行表征的第一步，检查了 EBV 基因表达和 EBV 阳性 DLBCL 系 Farage 对 IL-21 的敏感性。令人惊讶的是，尽管 c-Myc 上调，IL-21 诱导 Farage 细胞增殖而非凋亡。表达显性负效 EBNA1 突变体并随后下调 EBV 基因表达拮抗了 IL-21 诱导的 Farage 增殖并增加了凋亡。这些发现揭示了 EBV 在 DLBCL 中的一个以前未知的作用，这对于当前尝试使用 IL-21 进行治疗可能具有重要意义。
