title: Oncostatin M activates stat DNA binding and transcriptional activity in primary human fetal astrocytes: low- and high-passage cells have distinct patterns of stat activation.
abstract: In this study we explored the activation of the JAK/Stat pathway by gp 130 family cytokines in primary human astrocytes. We report that of four gp 130 cytokines tested, only oncostatin M (OnM) resulted in the activation of Stat molecules. To test that the induced molecules were transcriptionally active, transcription from a Stat-responsive reporter plasmid (from the acute-phase gene alpha-2 macroglobulin) transiently transfected into astrocytes was assessed after activation by OnM and was blocked by cotransfection with dominant-negative Stat3 encoding plasmids strongly suggesting that the activation was Stat-mediated. While DNA binding complexes comprised of both Stat1 and Stat3 were induced in low-passage cells, only those containing Stat3 were formed by extracts from high-passage cells. Stat1 protein was detected in the cytoplasm of high-passage cells indicating that the inability to form SIF-B and -C complexes was due to a lack of activation of Stat1 rather than a lack of expression. These results indicate a fundamental difference between low- and high-passage astrocytes in response to cytokine treatment that might result in distinct patterns of gene expression through altered ratios of activated Stat3 and Stat1.
authors.affiliation: Department of Neurosurgery, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Schaefer
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: T S
authors.initials: TS
authors.lastname: Schaefer
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D004789:Enzyme Activation; D005799:Genes, Dominant; D017930:Genes, Reporter; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000511:alpha-Macroglobulins / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C508351:OSM protein, human; D010455:Peptides; D020574:Proto-Oncogene Proteins c-sis; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D000511:alpha-Macroglobulins; D053683:Oncostatin M; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D001616:beta-Galactosidase