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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
Author(s) -
Caldwell Jerry,
Emerson Stephen G.
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041590205
Subject(s) - stromal cell , tumor necrosis factor alpha , bone marrow , biology , cytokine , colony stimulating factor , granulocyte macrophage colony stimulating factor , myeloid , immunology , microbiology and biotechnology , cell culture , cancer research , stem cell , haematopoiesis , genetics
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.