Differentiation associated modulation of the cytokine and chemokine expression pattern in human myeloid cell lines

Hematopoietic progenitor cell differentiation is associated with the expres sion of different sets of genes including those encoding membrane bound mol ecules and cytokines. While expression of the former has meticulously been linked to both lineage specificity and maturation stages and is routinely u sed in the diagnosis of human leukemias, the production of cytokines has no t systematically been analyzed in this respect. Secretion of cyto- and chem okines by HPC has been discussed as a key element of autocrine regulation o f cell differentiation and proliferation in normal and malignant hematopoie tic cells. Hematopoietic cell lines and their in vitro generated mature pro geny were used as a model to investigate the cytokine and chemokine express ion pattern prior to and after induction of differentiation. We show that a variety of cytokines are produced by these cells either constitutively or upon stimulation. Low levels of TNF-alpha and IL-8 were widely expressed by immature and mature cells, while peak values of TNF-alpha were detected in promyelocytic NB4 cells, as reported previously. Induction of monocytic di fferentiation by various agents was associated with upregulation of IL-1 be ta and IL-1ra expression, while a differentiation shift to the granulocytic lineage in the presence of retinoic acid (RA) led to a marked increase of macrophage chemoattractant protein-1 (MCP-1) producing cells. These data in dicate that lineage determination as well as maturation of hematopoietic ce lls may not only be associated with expression of specific surface molecule s but also with a distinct cytokine expression pattern. Further studies are necessary to show if this holds true for primary leukemic and normal hemat opoietic cells. (C) 2001 Elsevier Science Ltd. All rights reserved.