DIFFERENTIAL KINETICS OF POLYPEPTIDE EXPRESSION AND DIFFERENT BIOLOGICAL-ACTIVITIES IN THE HUMAN FIBROBLAST RESPONSE TO DSRNA OR INTERFERONTREATMENT

Using two-dimensional electrophoresis on total and nuclear extracts of human fibroblasts, we compared polypeptide patterns of cells treated with interferon-beta (IFN-beta), IFN-gamma, or with dsRNA in the prese nce of anti-IFN antibodies. The analysis of whole-cell extracts reveal ed that, after a 6-h treatment, the three agents induce the synthesis of a common set of proteins in addition to others that are specificall y induced either by IFNs or by dsRNA. After a 15-h treatment, this com mon set of proteins was only induced by IFNs. Furthermore, at this tim e, IFNs also regulated proteins whose synthesis was specifically induc ed or repressed by poly(I) . poly(C) in the 6-h treated cells. These r esults indicate that poly(I) - poly(C) regulates protein expression mo re rapidly and more transiently than IFNs. The analysis of nuclear ext racts showed similar differential kinetics of protein expression. Howe ver, a greater number of polypeptides was found to have their synthesi s specifically induced by dsRNA. Moreover, poly(I) . poly(C) was found to be mitogenic in these cells and did not induce a significant resis tance to vesicular stomatitis virus (VSV). This study provides evidenc e for an overlap in the expression of proteins by dsRNA and IFNs, alth ough these compounds do not share the same biological activities.