CYTOKINE GENE-EXPRESSION AND SYNTHESIS BY HUMAN MEGAKARYOCYTIC CELLS

Cytokine expression and production by human megakaryocytic cells were studied using the CMK cell line as a model for cytokine gene expression by polymerase chain reaction (PCR) and for cytokine protein synthesis by specific radioimmunoassays. CMK cells at all stages of maturation were found to constitutively express moderate mRNA levels for tumor necrosis factor (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin (IL) 1-beta, and endothelial cell growth factor (ECGF) transcripts. After 6-h treatment with the phorbol ester PMA, gene expression for IL-1-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and the IL-6 receptor were increased. After 24 h of exposure to PMA, levels for most cytokines declined to baseline, except for IL-6 which appeared as a new transcript. PMA-stimulated CMK lines synthesized low levels of TNF-alpha and IL-6, and higher levels of GM-CSF, IL-1-beta, and IL-1-alpha protein. These observations suggest that cells of megakaryocytic lineage are capable of producing a repertoire of cytokines which could mediate an autocrine role as well as modulate the replication and function of other hematopoietic cells.