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A signal through 4‐1BB ligand inhibits receptor for activation of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis by increasing interferon (IFN)‐beta production
Author(s) -
Shin Hyun-Hee,
Lee Eun-A,
Kim Soo-Jin,
Kwon Byoung S.,
Choi Hye-Seon
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.091
Subject(s) - rankl , microbiology and biotechnology , activator (genetics) , chemistry , receptor , interferon , biology , biochemistry , immunology
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.