Induced and Down-Regulated Proteins in the Human Cultured Hairy Cell Leukemia Line JOK-1 and the Burkitt's Lymphoma Cell Line Daudi During Incubation with Interferon-α: A Kinetic Study

Abstract

To elucidate the mechanism of action of interferon-α (IFN-α), the effect on cell proliferation and protein synthesis in the human hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi were investigated. While Daudi cells were inhibited in proliferation and in total protein synthesis, no effect was seen on JOK-1 cells. However, high-resolution two-dimensional gel electrophoresis showed that four polypeptides were induced in JOK-1 cells after IFN-α incubation, while an additional 11 were induced and two down-regulated in Daudi cells. Kinetic studies revealed that the changes in JOK-1 cells were only temporary (within 8–16 h) and small to moderate in magnitude (less than four-fold). In Daudi cells, the changes for two of these polypeptides were early (within 2 h), for most of them prolonged (at least 24 h), and for three of them of great magnitude (between 6- and 30-fold). Quantitative analytical assessments indicated that four IFN-α-inducible polypeptides, present in low amounts of untreated cells, were highly expressed only in sensitive Daudi cells upon IFN-α treatment. This observation might indicate a role for these polypeptides in the inhibition of cell proliferation in Daudi cells. Furthermore, six of the other IFN-α-modulated polypeptides were synthesized constitutively in JOK-1 cells at levels comparable to those achieved in IFN-α-treated Daudi cells. Since one of these constitutively synthesized polypeptides (i4, highly homologous to bovine tryptophanyl-tRNA synthetase and rabbit peptide chain-release factor) seems to be differently expressed during B-lymphocytic maturation, this observation might suggest a role for IFN-α and this polypeptide in cell differentiation. This observation, furthermore, shows that, in Daudi, IFN-α targets a polypeptide (i4) involved in the protein-synthesizing machinery, and this might be a step in the cell growth regulatory actions of this cytokine.

Taken together, our results indicate that the JOK-1 hairy cell line is insensitive to the antiproliferative activity of IFN-α. However, this study points out IFN-α-modulated polypeptides of interest for characterization in future investigation of cell proliferation and differentiation.