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 St at molecules. To test that the induced molecules were transcriptionally act ive, 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 act ivation was Stat-mediated. While DNA binding complexes comprised of both St at1 and Stat3 were induced in low-passage cells, only those containing Stat 3 were formed by extracts from high-passage cells, Stat1 protein was detect ed 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. (C) 2000 Academic Press.