Interferon-alpha 2b and vesnarinone influence levels of tumor necrosis factor-alpha, apoptosis, or interleukin 6 in ESKOL, a hairy cell leukemic cell line. A potential cytokine and oncogene relationship regulating apoptosis is suggested.
The in vitro effects of interferon-alpha (IFN) on levels of secreted interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF alpha), and nuclear matrix proteins (NMP) were examined in ESKOL, a B-lymphoblastoid cell line resembling hairy cell leukemia (HCL). IFN enhances differentiation in ESKOL, decreases TNF alpha levels, decreases apoptosis, increases IL-6 levels, and down regulates the expression of several oncogenes. Vesnarinone (Ves), a TNF alpha repressor, lowers TNF-alpha and decreases apoptosis in the same cell line. ESKOL exhibits enhanced apoptosis and reduced B-cell lymphomas (Bcl-2) levels over WIL-2. IL-6 and TNFalpha have been shown to decrease and increase apoptosis in B-cells respectively; however, treatment of ESKOL with these cytokines had no significant effect on apoptosis. We suggest that IFN decreases apoptosis by mechanisms involving enhanced IL-6 and Bcl-2 levels, decreased TNF alpha and the down regulation of apoptotic oncogenes, including c-myc.
Khalaf
Waleed
W
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46222, USA.
Maina
Caroline
C
Byers
Joseph
J
Harvey
William
W
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D019254:Genes, bcl-2; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007943:Leukemia, Hairy Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009857:Oncogenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015850:Interleukin-6; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D011804:Quinolines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C041667:vesnarinone