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.
Jenab
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Population Council, New York, New York 10021, USA.
Morris
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PL
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016762:Genes, fos / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D012708:Sertoli Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma