Effects of lipid mediators on the synthesis of leukaemia inhibitory factor and interleukin 6 by human bone marrow stromal cells.
Human bone marrow stromal cells regulate haematopoiesis by releasing cytokines such as leukaemia inhibitory factor (LIF) and interleukin 6 (IL-6). We have investigated the effects of 5 lipid mediators (i.e. 12-HETE, 15-HETE, platelet-activating factor (PAF), LTB4 and prostaglandin E2 (PGE2)) on their LIF and IL-6 synthesis. 12-HETE, 15-HETE and LTB4 (both at 1 microM) stimulate the LIF production by human bone marrow stromal cells grown in 10% fetal calf serum (FCS). In contrast, PAF and PGE2 have no effect. 12-HETE (1 microM) enhances LIF synthesis in serum free medium 7.7-fold and stimulates IL-1 induced LIF production. 12-HETE, 15-HETE, PAF and LTB4 have no effect on the spontaneous, serum- and cytokine-induced IL-6 synthesis by bone marrow stromal cells. In contrast PGE2 significantly stimulates serum-induced IL-6 synthesis. This study reports for the first time that lipid mediators may act on human haematopoiesis by modulating LIF and IL-6 synthesis by bone marrow stromal cells. Particularly, 12-HETE enhances LIF but not IL-6 synthesis. The different regulation of IL-6 and LIF synthesis in response to lipid mediators highlights the complexity of the cytokine regulation into the human bone marrow.
Denizot
Y
Y
Laboratoire d'Hématologie Expérimentale, Faculté de Médecine, 2 rue Dr. Marcland, 87025 Limoges, France.
Trimoreau
F
F
Praloran
V
V
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D015232:Dinoprostone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D053605:Leukemia Inhibitory Factor; D007975:Leukotriene B4 / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis*; D010972:Platelet Activating Factor / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D006131:Growth Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008055:Lipids; D008222:Lymphokines; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D015232:Dinoprostone