The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 184K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Udagawa, N.
Right arrow Articles by Gillespie, M. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Udagawa, N.
Right arrow Articles by Gillespie, M. T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1997/3/1005/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 6, March 17, 1997 1005-1012

Articles

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

Nobuyuki Udagawa*, Nicole J. Horwood*, Jan Elliott*, Alan Mackay{ddagger}, Jane Owens{ddagger}, Haruki Okamura§, Masashi Kurimoto, Timothy J. Chambers{ddagger}, T. John Martin*, and Matthew T. Gillespie*

From the * St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia; {ddagger} Department of Histopathology, St. George's Hospital Medical School, London SW17 ORE, United Kingdom; § Department of Bacteriology, Hyogo College of Medicine, Nishinomiya 663, Japan; and Fujisaki Institute, Hayashibara Biochemical Laboratories Incorporated, Okayama 702, Japan

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 1{alpha},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.

Address correspondence to Dr. M.T. Gillespie, St. Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy 3065, Victoria, Australia.

M.T. Gillespie is a Research Fellow of the NHMRC Australia and N. Udagawa was a recipient of a C.R. Roper Fellowship from The University of Melbourne.

N. Udagawa and N.J. Horwood contributed equally to this work.

1 Abbreviations used in this paper: 1{alpha},25(OH)2 D3, 1{alpha},25-dihydroxyvitamin D3; {alpha}GM–CSF, neutralizing antibody to GM–CSF; {alpha}IFN-{gamma}, neutralizing antibody to IFN-{gamma}; ddPCR, differential display PCR; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GM–CSF, granulocyte/macrophage colony-stimulating factor; IFN-{gamma} R–/–, IFN-{gamma} receptor type II knockout; IGIF, interferon-{gamma}-inducing factor; OCL, osteoclast-like multinucleated cells; PGE2, prostaglandin E2; PTH, parathyroid hormone; RT, reverse transcription (or transcribed); TRAP, tartrate resistant acid phosphatase.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS