INTERFERON-GAMMA INDUCES THE EXPRESSION OF IMMEDIATE-EARLY GENES C-FOS AND C-JUN IN ASTROCYTES

The expression of the proto-oncogenes, c-fos and c-jun, in cultured mo use astrocytes and its induction by the potent astrocyte activator int erferon-gamma (IFN-gamma), were examined by Northern blot and flow cyt ometry. Both proto-oncogenes were induced in a dose-dependent manner, peaking around 100 U/ml of IFN-gamma. The kinetics of expression is ve ry transient for c-fos, reaching a maximum at 30 min and decreasing ra pidly thereafter. The c-jun remained high throughout the stages analys ed. Cycloheximide superinduced c-fos and c-jun induction by IFN-gamma, thus indicating that both act as immediate early genes. The products of c-fos and c-jun, proteins FOS and JUN, that act in conjunction form ing the regulatory factor AP-1, were detected 1 hr after stimulation i n virtually all cells, using flow cytometry. The induction in astrocyt es of both proto-oncogenes could be the first stage of immunological a ctivation of these central nervous system cells by immune interferon.