Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells

Leukaemia inhibitory factor (LIF) acts on the growth and differentiation of haematopoietic cells, By using a specific enzyme-linked immunosorbent assay for human LIF, we demonstrate that human bone marrow stromal cells produce LIF, LIF synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly 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-stimulating factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growth factor (bFGF), platelet-activating factor (PAF), protaglandin E-2 (PGE(2)), leukotriene B-4 (LTB4, and leukotriene C-4 (LTC4) did not, These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of LIF inside human bone marrow. (C) 1997 Academic Press Limited.