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.

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. Copyright 2000 Academic Press.