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Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist.
Blood 1994; 84(12):4142-50Blood

Abstract

We investigated the effects of interferon-alpha (IFN-alpha) on the expression of cytokines by human bone marrow stromal cells. Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and interleukin-1 beta (IL-1 beta) in stromal cell layers was induced by incubation with IL-1 alpha, tumor necrosis factor (TNF), or lipopolysaccharide (LPS). Addition of IFN-alpha to such stimulated cultures resulted in a strong downregulation of mRNA expression of GM-CSF and IL-1 beta. Similarly, the protein levels of GM-CSF and IL-1 beta were significantly reduced by IFN-alpha, whereas G-CSF production was only moderately inhibited. In contrast, IFN-alpha markedly stimulated the production of IL-1 receptor antagonist (IL-1RA) by stromal cells. The inhibition of cytokine expression resulted in a reduced hematopoietic activity of stromal cells, indicated by a reduced proliferation of the factor dependent cell line MO7e on IFN-alpha-treated stromal cells. In the presence of cycloheximide (CHX), IFN-alpha failed to inhibit IL-1 mRNA expression, whereas the regulation of GM-CSF and IL-1RA by IFN-alpha was not affected. Our results indicate that the myelosuppressive effects of IFN-alpha, as observed in therapeutic applications or associated with viral infections, are, in part, indirectly mediated by inhibition of the paracrine production of hematopoietic growth factors.

Authors+Show Affiliations

Third Department of Medicine, Johannes Gutenberg University School of Medicine, Mainz, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7994029

Citation

Aman, M J., et al. "Regulation of Cytokine Expression By Interferon-alpha in Human Bone Marrow Stromal Cells: Inhibition of Hematopoietic Growth Factors and Induction of Interleukin-1 Receptor Antagonist." Blood, vol. 84, no. 12, 1994, pp. 4142-50.
Aman MJ, Keller U, Derigs G, et al. Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist. Blood. 1994;84(12):4142-50.
Aman, M. J., Keller, U., Derigs, G., Mohamadzadeh, M., Huber, C., & Peschel, C. (1994). Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist. Blood, 84(12), pp. 4142-50.
Aman MJ, et al. Regulation of Cytokine Expression By Interferon-alpha in Human Bone Marrow Stromal Cells: Inhibition of Hematopoietic Growth Factors and Induction of Interleukin-1 Receptor Antagonist. Blood. 1994 Dec 15;84(12):4142-50. PubMed PMID: 7994029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist. AU - Aman,M J, AU - Keller,U, AU - Derigs,G, AU - Mohamadzadeh,M, AU - Huber,C, AU - Peschel,C, PY - 1994/12/15/pubmed PY - 1994/12/15/medline PY - 1994/12/15/entrez SP - 4142 EP - 50 JF - Blood JO - Blood VL - 84 IS - 12 N2 - We investigated the effects of interferon-alpha (IFN-alpha) on the expression of cytokines by human bone marrow stromal cells. Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and interleukin-1 beta (IL-1 beta) in stromal cell layers was induced by incubation with IL-1 alpha, tumor necrosis factor (TNF), or lipopolysaccharide (LPS). Addition of IFN-alpha to such stimulated cultures resulted in a strong downregulation of mRNA expression of GM-CSF and IL-1 beta. Similarly, the protein levels of GM-CSF and IL-1 beta were significantly reduced by IFN-alpha, whereas G-CSF production was only moderately inhibited. In contrast, IFN-alpha markedly stimulated the production of IL-1 receptor antagonist (IL-1RA) by stromal cells. The inhibition of cytokine expression resulted in a reduced hematopoietic activity of stromal cells, indicated by a reduced proliferation of the factor dependent cell line MO7e on IFN-alpha-treated stromal cells. In the presence of cycloheximide (CHX), IFN-alpha failed to inhibit IL-1 mRNA expression, whereas the regulation of GM-CSF and IL-1RA by IFN-alpha was not affected. Our results indicate that the myelosuppressive effects of IFN-alpha, as observed in therapeutic applications or associated with viral infections, are, in part, indirectly mediated by inhibition of the paracrine production of hematopoietic growth factors. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/7994029/Regulation_of_cytokine_expression_by_interferon_alpha_in_human_bone_marrow_stromal_cells:_inhibition_of_hematopoietic_growth_factors_and_induction_of_interleukin_1_receptor_antagonist_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=7994029 DB - PRIME DP - Unbound Medicine ER -