title: Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3.
abstract: Extranodal, nasal NK/T-cell lymphomas are regularly Epstein-Barr virus (EBV)-positive, with a type II latency pattern, expressing thus EBNA-1 and LMP1. The contribution of EBV to the tumor development is not known. Similarly to normal natural killer (NK) cells, cell lines derived from malignancies with a NK phenotype require IL-2 for in vitro proliferation. In our effort to explore the contribution of EBV, particularly the role of the LMP1 protein, to the pathogenesis of the NK lymphoma we found that its expression, studied in the NK-lines SNK6 and KAI3, depended on the supply of IL-2 or other cytokines. In the absence of IL-2 other cytokines, such as IL-10 and IFN-gamma, could maintain LMP1, but the cells did not proliferate. When grown in IL-2, the SNK6 cells produced IL-10 and IFN-gamma, and these cytokines mediated the expression of LMP1. IL-10 treatment enhanced, while IFN-gamma receptor blocking antibody reduced, the expression of CD25 and CD54 in the EBV-positive, but not in the EBV-negative lines. IL-10 treated cells required lower amount of IL-2 for proliferation compared to the untreated cells. This effect was seen only with the EBV-positive NK lines in which LMP1 and CD25 were concomitantly upregulated. By this mechanism EBV could have an important role in the development of NK lymphoma since the inflammatory component in the tumor tissue can provide these cytokines.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. miki.takahara@mtc.ki.se
authors.forename: Miki
authors.initials: M
authors.lastname: Takahara
authors.forename: Loránd L
authors.initials: LL
authors.lastname: Kis
authors.forename: Noémi
authors.initials: N
authors.lastname: Nagy
authors.forename: Anquan
authors.initials: A
authors.lastname: Liu
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.forename: George
authors.initials: G
authors.lastname: Klein
authors.forename: Eva
authors.initials: E
authors.lastname: Klein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies / Q000494:pharmacology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D004854:Herpesvirus 4, Human / Q000254:growth & development / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D060588:LIM Domain Proteins; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D003598:Cytoskeletal Proteins; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016753:Interleukin-10; D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D000096743:Interferon gamma Receptor; C484380:PDLIM7 protein, human; C494079:STAT1 protein, human; C494086:STAT3 protein, human