Lipid mediators modulate the synthesis of interleukin 8 by human bone marrow stromal cells

Bone marrow stromal cells regulate marrow haematopoiesis by secreting inter leukins (IL) such as IL-8, Lipid mediators modulate IL-8 synthesis in numer ous cell types. We have investigated the effects of 5 lipid mediators (PAF, PGE(2), LTB4, 12-HETE and 15-HETE) on the spontaneous and cytokine-induced IL-8 synthesis by human bone marrow stromal cells. By using reverse-transc riptase polymerase chain reaction (RT-PCR) we demonstrate that these cells constitutively express IL-8 transcripts, By using a specific ELISA, we foun d that the production of IL-8 by marrow stromal cells is enhanced after sti mulation with 12-HETE (1 mu M) both in serum-free and serum-containing cult ure medium. LTB4 (1 mu M) enhances IL-8 production only in serum-supplement ed medium. PAF, PGE(2) and 15-HETE (1 mu M to 0.1 nM) have no effect on the spontaneous and serum-induced production of IL-8 by human bone marrow stro mal cells. PGE(2) (1 mu M or 10 nM) reduces marrow stromal cell IL-8 synthe sis in response to IL-1 alpha or TNF-alpha. In contrast, PAF, 12-HETE, 15-H ETE and LTB4 have no effect. In conclusion, various lipid mediators modulat e the spontaneous, serum- or cytokine-induced IL-8 synthesis by bone marrow stromal cells, highlighting, for the first time, their potential role in t he regulation of IL-8 production within the human bone marrow. (C) 1999 Aca demic Press.