A Signal Through 4-1bb Ligand Inhibits Receptor for Activation of Nuclear Factor-kappab Ligand (Rankl)-induced Osteoclastogenesis by Increasing Interferon (Ifn)-beta Production.
From: Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Republic of Korea.
FEBS letters
- Publish Date: Mar 2006
- ISSN: 0014-5793
- Volume: 580
- Issue: 6
- Pages: 1601-6
- Medium: Print
- Language: English
- Citation (JAMA): Shin Hyun-Hee, Lee Eun-A, Kim Soo-Jin, et al. A Signal Through 4-1bb Ligand Inhibits Receptor for Activation of Nuclear Factor-kappab Ligand (Rankl)-induced Osteoclastogenesis by Increasing Interferon (Ifn)-beta Production.. FEBS Lett. Mar 2006;580:1601-6
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-kappaB 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)-beta in BMM and neutralization of IFN-beta 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-beta in BMM.
Mesh Headings (Keywords): 4-1BB Ligand, Animals, Bone and Bones, Carrier Proteins, Cell Differentiation, Humans, Immunoglobulin Fc Fragments, Interferon-beta, Macrophage Colony-Stimulating Factor, Macrophages, Membrane Glycoproteins, Mice, Mice, Mutant Strains, NF-kappa B, Osteoclasts, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Recombinant Fusion Proteins, Signal Transduction, Tumor Necrosis Factors, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16480981
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