Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antigens, Nuclear
-
Antineoplastic Agents / pharmacology*
-
Apoptosis / drug effects*
-
Apoptosis / genetics
-
Gene Expression Regulation, Leukemic / drug effects*
-
Genes, bcl-2
-
Humans
-
Interferon alpha-2
-
Interferon-alpha / pharmacology*
-
Interleukin-6 / biosynthesis*
-
Interleukin-6 / metabolism
-
Leukemia, Hairy Cell / genetics
-
Leukemia, Hairy Cell / metabolism
-
Leukemia, Hairy Cell / pathology*
-
Nuclear Proteins / biosynthesis
-
Nuclear Proteins / genetics
-
Oncogenes
-
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
-
Pyrazines
-
Quinolines / pharmacology*
-
Recombinant Proteins
-
Tumor Cells, Cultured / drug effects
-
Tumor Cells, Cultured / metabolism
-
Tumor Necrosis Factor-alpha / biosynthesis*
-
Tumor Necrosis Factor-alpha / metabolism
Substances
-
Antigens, Nuclear
-
Antineoplastic Agents
-
Interferon alpha-2
-
Interferon-alpha
-
Interleukin-6
-
Nuclear Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
Pyrazines
-
Quinolines
-
Recombinant Proteins
-
Tumor Necrosis Factor-alpha
-
vesnarinone