STAT3 exerts two-way regulation in the biological effects of IL-6 in M1 leukemia cells

The signal transducer and activator of transcription (STAT) proteins have b een implicated in cytokine-regulated proliferation, differentiation and cel l survival. Interleukin-6 (IL-6). a pleiotropic cytokine, induces a robust and sustained activation of STAT3 in M1 acute myeloid leukemia cells. which in turn undergo growth arrest, terminal differentiation and apoptosis in r esponse to IL-6. The roles of STAT3 activation in IL-6-mediated responses i n M1 cells are not fully understood. We introduced STAT3 antisense cDNA int o M1 cells. STAT3 antisense cDNA blocked the expression and IL-6-induced ty rosine phosphorylation and DNA binding of STAT3. and resulted in reduction of both IL-6-induced growth arrest at G(0)/G(1) phase and macrophage differ entiation in the M1 transformants. This observation is in accordance with p revious reports and confirms that STAT3 plays an essential role in IL-6-ind uced growth arrest and terminal differentiation in MI leukemia cells. On th e other hand, STAT3 antisense cDNA auizmented IL-6-induced apoptosis of MI cells, which was supported by the cell cycle assay. DNA fragmentation assay and detection of the p17 active fragment of Caspase 3. As proliferation in hibition and differentiation induction stands for a negative signal, while survival maintenance stands for a positive signal. we conclude that STAT3 e xerts two-way regulation on the biological effects of IL-6 in M1 leukemia c ells. (C) 2001 Elsevier Science Ltd. All rights reserved.