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

✍ Scribed by Jerry Caldwell; Stephen G. Emerson

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 855 KB
• Volume: 159
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041590205

✦ Synopsis

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 I L -l a and TNFa act synergistically to stimulate GM-CSF and G-CSF production by cultured marrow stromal cells. We further show that I L -l a and TNFa 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 I L -l a and TNFa have an unequal ability to induce myeloid-CSF production by both cultures, with I L -l a being the more potent inducer. We found that induction by I L -l a and TNFa was independent of cell proliferation. The effect of I L -l a and TNFa on production of the two myeloid-CSFs by the clonal cells was significantly greater than the unfractionated passaged strornal 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-la and TNFa, 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. o 1994 ~i l e y -~i s s , Inc.