SPONTANEOUS AND INDUCIBLE PRODUCTION OF LEUKEMIA INHIBITORY FACTOR BYHUMAN BONE-MARROW STROMAL CELLS

Leukaemia inhibitory factor (LIF) acts on the growth and differentiati on of haematopoietic cells, By using a specific enzyme-linked immunoso rbent assay for human LIF, we demonstrate that human bone marrow strom al cells produce LIF, LIF synthesis is enhanced in a dose-dependent ma nner after stimulation with lipopolysaccharide (LPS) and phorbol 12-my ristate 13-acetate (PMA), LIF production in response to PMA is PKC-dep endent since the two PKC inhibitors sphingosine and staurosporine mark edly diminished it, Interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-3, IL-6, IL-8, tumour necrosis factor (TNF-alpha) and SCF (both at 10 ng /ml) stimulate LIF production, By contrast macrophage colony-stimulati ng factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growt h factor (bFGF), platelet-activating factor (PAF), protaglandin E-2 (P GE(2)), leukotriene B-4 (LTB4, and leukotriene C-4 (LTC4) did not, The se results suggest that bone marrow stromal cells might represent a ma jor source for the cytokine-regulated local production of LIF inside h uman bone marrow. (C) 1997 Academic Press Limited.