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 (PMAS). LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly diminished it. Interleukin 1alpha (IL-1alpha), IL-1beta, 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 E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4 (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.
Lorgeot
V
V
Laboratoire d'Hématologie Expérimentale,, Faculté de Médecine, 2 rue Dr. Marcland, Limoges, 87025, France.
Rougier
F
F
Fixe
P
P
Cornu
E
E
Praloran
V
V
Denizot
Y
Y
D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides; D008222:Lymphokines; D013755:Tetradecanoylphorbol Acetate