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

Bone marrow stromal cells regulate marrow haematopoiesis by secreting interleukins (IL) such as IL-8, Lipid mediators modulate IL-8 synthesis in numerous 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-transcriptase polymerase chain reaction (RT-PCR) we demonstrate that these cells constitutively express IL-8 transcripts, By using a specific ELISA, we found that the production of IL-8 by marrow stromal cells is enhanced after stimulation with 12-HETE (1 mu M) both in serum-free and serum-containing culture medium. LTB4 (1 mu M) enhances IL-8 production only in serum-supplemented 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 stromal cells. PGE(2) (1 mu M or 10 nM) reduces marrow stromal cell IL-8 synthesis in response to IL-1 alpha or TNF-alpha. In contrast, PAF, 12-HETE, 15-HETE and LTB4 have no effect. In conclusion, various lipid mediators modulate the spontaneous, serum- or cytokine-induced IL-8 synthesis by bone marrow stromal cells, highlighting, for the first time, their potential role in the regulation of IL-8 production within the human bone marrow. (C) 1999 Academic Press.