IL-1Α and TNFΑ act synergistically to stimulate production of myeloid colony-stimulating factors by cultured human bone marrow stromal cells and cloned stromal cell strains

Abstract

Human bone marrow stromal cells repond to stimulation by the monokines IL-1 and TNF by producing colony-stimulating factors such as GM-CSF and G-CSF. In this study we show that IL-1Α and TNFΑ act synergistically to stimulate GM-CSF and G-CSF production by cultured marrow stromal cells. We further show that IL-1Α and TNFΑ synergistically stimulate production of GM-CSF and G-CSF by a clonal stroma-derived cell strain. Although IL-1 and TNF share many of the same biological activities, we show that IL-1Α and TNFΑ have an unequal ability to induce myeloid-CSF production by both cultures, with IL-1Α being the more potent inducer. We found that induction by IL-1Α and TNFΑ was independent of cell proliferation. The effect of IL-1Α and TNFΑ on production of the two myeloid-CSFs by the clonal cells was significantly greater than the unfractionated passaged stromal cultures, having the greater effect on G-CSF production. The clonally derived stromal cells constitutively produced colony-stimulating activity, in particular GM-CSF, at levels easily detected by ELISA. These findings show that, in addition to the overlapping and additive activities of IL-1Α and TNFΑ, they can interact synergistically. Our findings further suggest that a small subpopulation of stroma cells may be the major producer of G-CSF in the marrow microenvironment during immune response. © 1994 wiley-Liss, Inc.