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Udagawa, Nobuyuki, Horwood, Nicole J. 
ORCID: https://orcid.org/0000-0002-6344-1677, Elliott, Jan, Mackay, Alan, Owens, Jane, Okamura, Haruki, Kurimoto, Masashi, Chambers, Timothy J., Martin, T. John and Gillespie, Matthew T.
(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).
pp. 1005-1012.
ISSN 0022-1007
Abstract
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 |
|---|---|
| Uncontrolled Keywords: | animals,animals, newborn,base sequence,bone marrow cells,drug effects,coculture techniques,biosynthesis,pharmacology,pharmacology,pharmacology,interleukin-18,male,mice,mice, inbred c57bl,mice, knockout,molecular sequence data,cytology,cytology,polymerase chain reaction,biosynthesis,deficiency,recombinant proteins,transcription, genetic |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 06 Mar 2019 09:30 |
| Last Modified: | 19 Oct 2023 02:22 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/70112 |
| DOI: |
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