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Interleukin-18 (interferon-gamma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteoclast formation

Udagawa, N; Horwood, NJ; Elliott, J; Mackay, A; Owens, J; Okamura, H; Kurimoto, M; Chambers, TJ; Martin, TJ; Gillespie, MT (1997) Interleukin-18 (interferon-gamma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteoclast formation. JOURNAL OF EXPERIMENTAL MEDICINE, 185 (6). 1005 - 1012. ISSN 0022-1007
SGUL Authors: Chambers, Timothy John

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We have established by differential display polymerase chain reaction of mRNA that interleukin (IL)-18 is expressed by osteoblastic stromal cells. The stromal cell populations used for comparison differed in their ability to promote osteoclast-like multinucleated cell (OCL) formation. mRNA for IL-18 was found to be expressed in greater abundance in lines that were unable to support OCL formation than in supportive cells. Recombinant IL-18 was found to inhibit OCL formation in cocultures of osteoblasts and hemopoietic cells of spleen or bone marrow origin. IL-18 inhibited OCL formation in the presence of osteoclastogenic agents including 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, parathyroid hormone, IL-1, and IL-11. The inhibitory effect of IL-18 was limited to the early phase of the cocultures, which coincides with proliferation of hemopoietic precursors. IL-18 has been reported to induce interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF) production in T cells, and both agents also inhibit OCL formation in vitro. Neutralizing antibodies to GM-CSF were able to rescue IL-18 inhibition of OCL formation, whereas neutralizing antibodies to IFN-gamma did not. In cocultures with osteoblasts and spleen cells from IFN-gamma receptor type II-deficient mice, IL-18 was found to inhibit OCL formation, indicating that IL-18 acted independently of IFN-gamma production: IFN-gamma had no effect in these cocultures. Additionally, in cocultures in which spleen cells were derived from receptor-deficient mice and osteoblasts were from wild-type mice and vice versa, we identified that the target cells for IFN-gamma inhibition of OCL formation were the hemopoietic cells. The work provides evidence that IL-18 is expressed by osteoblasts and inhibits OCL formation via GM-CSF production and not via IFN-gamma production.

Item Type: Article
Additional Information: © 1997 Rockefeller University Press BPublished under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License.
Keywords: Animals, Animals, Newborn, Base Sequence, Bone Marrow Cells, Cell Differentiation, Coculture Techniques, Cytokines, Granulocyte-Macrophage Colony-Stimulating Factor, Interferon-gamma, Interleukin-11, Interleukin-18, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Osteoblasts, Osteoclasts, Polymerase Chain Reaction, RNA, Messenger, Receptors, Interferon, Recombinant Proteins, Transcription, Genetic, Science & Technology, Life Sciences & Biomedicine, Immunology, Medicine, Research & Experimental, Research & Experimental Medicine, IMMUNOLOGY, MEDICINE, RESEARCH & EXPERIMENTAL, BONE-MARROW CULTURES, CELL-FORMATION, IFN-GAMMA, DIFFERENTIATION, MOUSE, MICE, MODULATION, MACROPHAGE, RECEPTOR, RAT, Immunology, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
ISSN: 0022-1007
Related URLs:
17 March 1997Published
Web of Science ID: WOS:A1997WP40400004
Publisher's version:

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