Growth hormone-mediated transcriptional activation of the rat serine protease inhibitor 2.1 gene involves both interleukin-1 beta-sensitive and -insensitive pathways.
Growth hormone (GH)-dependent activation of the rat serine protease inhibitor 2.1 (spi 2.1) gene in vivo requires both a modification of the chromatin structure and the activation of transcription factors mediated by the tyrosine protein Janus kinase JAK2. To address the question of the relationship between those two GH effects, we used interleukin 1 beta (Il-1 beta) that was previously shown to inhibit spi 2.1 gene expression. In cultured hepatocytes from normal rats, Il-1 beta did not antagonize GH-dependent stimulation of promoter activity (i.e., in episomal constructs) mediated by transcription factors activated by JAK2. In hepatocytes from inflamed rats, GH triggered JAK2-dependent activation of transcription factors as in control cells but failed to stimulate genomic spi 2.1 gene expression. It thus appears that the Il-1 beta-insensitive activation of transcription factors by GH is independent of its action on the nucleosomal structure of the spi 2.1 gene which, in contrast, is sensitive to this cytokine.
Le Cam
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Institut National de la Santé et de la Recherche Médicale, INSERM 376, CHU Arnaud-de-Villeneuve, Montpellier, France. lecam@u376.montp.inserm.fr
Paul
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Thissen
J P
JP
D000818:Animals; D002478:Cells, Cultured; D019382:Human Growth Hormone / Q000235:genetics / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics; D007375:Interleukin-1 / Q000502:physiology*; D053614:Janus Kinase 2; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D009707:Nucleosomes / Q000187:drug effects / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects
D007375:Interleukin-1; C091103:LOC299282 protein, rat; D009687:Nuclear Proteins; D009707:Nucleosomes; D011518:Proto-Oncogene Proteins; D015842:Serine Proteinase Inhibitors; D019382:Human Growth Hormone; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2