IL-6 induces expression of the Fli-1 proto-oncogene via STAT3

Induction of gene expression by IL-6 has become an area of intense interest due to the role this cytokine plays in mediating aspects of inflammation, cellular differentiation, and proliferation. The ETS family of transcription factors represents a group of positive and negative regulators of transcription, that are differentially expressed in a cell and tissue specific manner. The ETS protein Fli-1 is known to induce differentiation in the erythroblastic leukemia cell line K562 along megakaryocytic developmental pathways. Here we show that IL-6 treatment of K562 induces the expression of Fli-1 via the STAT3 transcription factor. Upregulation of Fli-1 expression can be abrogated by the addition of AG490, a chemical inhibitor of JAK kinases, and by transfecting the cells with a dominant negative STAT3 expression construct.