IL-12 Alone and in Synergy with IL-18 Inhibits Osteoclast Formation In Vitro

  • Nicole J Horwood
    St. Vincent’s Institute of Medical Research , Fitzroy, Victoria ,
  • Jan Elliott
    St. Vincent’s Institute of Medical Research , Fitzroy, Victoria ,
  • T John Martin
    St. Vincent’s Institute of Medical Research , Fitzroy, Victoria ,
  • Matthew T Gillespie
    St. Vincent’s Institute of Medical Research , Fitzroy, Victoria ,

書誌事項

公開日
2001-04
権利情報
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.4049/jimmunol.166.8.4915
公開者
Oxford University Press (OUP)

この論文をさがす

説明

<jats:title>Abstract</jats:title> <jats:p>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-κB 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-γ R−/− mice, indicating that neither GM-CSF nor IFN-γ 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.</jats:p>

収録刊行物

被引用文献 (12)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ