A signal through 4‐1BB ligand inhibits receptor for activation of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis by increasing interferon (IFN)‐beta production
- 9 February 2006
- journal article
- Published by Wiley in FEBS Letters
- Vol. 580 (6) , 1601-1606
- https://doi.org/10.1016/j.febslet.2006.01.091
Abstract
We tested whether any intracellular signals are transmitted through 4‐1BB/CD137 ligand (4‐1BBL), using a 4‐1BB‐Fc fusion protein and 4‐1BB‐deficient mice. Immobilized 4‐1BB‐Fc fusion protein strongly inhibited osteoclastogenesis induced by macrophage colony‐stimulating factor (M‐CSF) and receptor activator of nuclear factor‐κB ligand (RANKL) derived from bone marrow macrophages (BMM). Incubation of BMM with M‐CSF increased 4‐1BBL mRNA and surface expression of 4‐1BBL protein. Cross‐linking 4‐1BBL with immobilized 4‐1BB‐Fc also dramatically reduced the number of tartrate‐resistant acid phosphatase (TRAP)‐positive multinuclear cells (MNC) derived from the BMM from 4‐1BB‐deficient mice, suggesting that the inhibitory effect of immobilized 4‐1BB on osteoclastogenesis is due to a signal through 4‐1BBL. Reverse signaling by 4‐1BB‐Fc increased the level of interferon (IFN)‐β in BMM and neutralization of IFN‐β reversed the inhibitory effect of immobilized 4‐1BB‐Fc. Inhibition of osteoclastogenesis by immobilized 4‐1BB‐Fc is, therefore, at least in part, due to elevation of the level of the negative regulator, IFN‐β in BMM.Keywords
This publication has 29 references indexed in Scilit:
- Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) stimulates osteoclast differentiation in response to receptor activator of NF-κB ligand (RANKL) in osteoclast cellsBone, 2005
- Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signalingNature Structural & Molecular Biology, 2004
- Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro OsteoclastogenesisPublished by Elsevier ,2004
- The soluble glucocorticoid-induced tumor necrosis factor receptor causes cell cycle arrest and apoptosis in murine macrophagesBiochemical and Biophysical Research Communications, 2004
- Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritisExperimental & Molecular Medicine, 2004
- Regulation of Receptor Activator of NF-κB Ligand-induced Osteoclastogenesis by Endogenous Interferon-β (INF-β) and Suppressors of Cytokine Signaling (SOCS)Journal of Biological Chemistry, 2002
- RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-βNature, 2002
- Interferon-γ Directly Inhibits TRANCE-Induced OsteoclastogenesisBiochemical and Biophysical Research Communications, 2000
- CD40 ligand-transduced co-stimulation of T cells in the development of helper functionNature, 1995
- The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and deathCell, 1994