Differential activation of signal transducer and activator of transcription (STAT)-3 and STAT-1 transcription factors and c-fos messenger ribonucleic acid by interleukin-6 and interferon-gamma in Sertoli cells

The regulation of expression of the immediate early gene c-fos messenger RNA (mRNA) by interleukin-6 (IL-6) and interferon-gamma (IFN gamma) was investigated using primary Sertoli cells established from immature rat testis. Using electrophoretic mobility shift assay, we show that IL-6 and IFN gamma predominantly activate signal transducers and activators of transcription-3 and -1 proteins after 15 min of treatment, respectively, whereas solution hybridization and Northern blot analyses show a differential induction of the c-fos mRNA by the two cytokines. IL-6 stimulated c-fos mRNA levels by 6-fold after 45 min; these levels returned to control values by 12 h of treatment. In contrast, IFN gamma increased c-fos message 2-fold transiently, with RNA at the control level by 2 h after treatment. These cytokine-dependent inductions of c-fos mRNA levels were not affected by cyclohexamide, but were diminished by actinomycin D pretreatments, consistent with regulation at the transcriptional level. The differential activation of this testicular c-fos gene thus suggests multiple mechanisms and/or pathways of cytokine regulation in Sertoli cells.