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
; 580(6): 1601-6, 2006 Mar 06.
Article
em En
| MEDLINE
| ID: mdl-16480981
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.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Osso e Ossos
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Glicoproteínas de Membrana
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Proteínas de Transporte
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Interferon beta
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Fatores de Necrose Tumoral
Limite:
Animals
/
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2006
Tipo de documento:
Article