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Horwood, Nicole J. 
ORCID: https://orcid.org/0000-0002-6344-1677, Elliott, Jan, Martin, T. John and Gillespie, Matthew T.
(2001)
IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro.
Journal of Immunology, 166 (8).
pp. 4915-4921.
ISSN 0022-1767
Abstract
IL-12, like IL-18, was shown to potently inhibit osteoclast formation in cultures of cocultures of murine osteoblast and spleen cells, as well as in adult spleen cells treated with M-CSF and receptor activator of NF-kappaB ligand (RANKL). Neither IL-12 nor IL-18 was able to inhibit RANKL-induced osteoclast formation in cultured RAW264.7 cells, demonstrating that IL-12, like IL-18, was unable to act directly on osteoclastic precursors. IL-12, like IL-18, was found to act by T cells, since depletion of T cells from the adult spleen cell cultures ablated the inhibitory action of IL-12 and addition of either CD4 or CD8 T cells from C57BL/6 mice to RANKL-stimulated RAW264.7 cultures permitted IL-12 or IL-18 to be inhibitory. Additionally, IL-12 was still able to inhibit osteoclast formation in cocultures with osteoblasts and spleen cells from either GM-CSF R(-/-) mice or IFN-gamma R(-/-) mice, indicating that neither GM-CSF nor IFN-gamma was mediating osteoclast inhibition in these cultures. Combined, IL-18 and IL-12 synergistically inhibited osteoclast formation at concentrations 20- to 1000-fold less, respectively, than when added individually. A candidate inhibitor could not be demonstrated using neutralizing Abs to IL-4, IL-10, or IL-13 or from mRNA expression profiles among known cytokine inhibitors of osteoclastogenesis in response to IL-12 and IL-18 treatment, although the unknown inhibitory molecule was determined to be secreted from T cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | animals,instrumentation,immunology,cell line,cells, cultured,coculture techniques,immunology,drug combinations,drug synergism,metabolism,metabolism,metabolism,metabolism,metabolism,male,mice,mice, inbred c57bl,mice, knockout,cytology,deficiency,deficiency,immunology |
| 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: | 25 Sep 2024 13:57 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/70120 |
| DOI: | 10.4049/jimmunol.166.8.4915 |
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