EBV counteracts IL-21-induced apoptosis in an EBV-positive diffuse large B-cell lymphoma cell line.
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.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. liang.wu@ki.se
Liang
L
Wu
Barbro
B
Ehlin-Henriksson
Hong
H
Zhu
Ingemar
I
Ernberg
George
G
Klein
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000098546:Interleukin-21
D019309:Epstein-Barr Virus Nuclear Antigens; D007378:Interleukins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000098546:Interleukin-21; C417029:EBV-encoded nuclear antigen 1