Induction of apoptosis in murine clonal osteoblasts expressed by human T-cell leukemia virus type I tax by NF-kappa B and TNF-alpha.
We investigated the effects of various cytokines in the presence of human T-cell leukemia virus type I (HTLV-I) tax protein in murine clonal osteoblasts, MC3T3-E1 cells. Skeletal remodeling by osteoclasts and osteoblasts is coordinated by cytokines, which are activated by HTLV-I tax protein via nuclear factor-kappa B (NF-kappa B). MC3T3-E1 cells were cocultured with an irradiated HTLV-I-producing lymphocyte cell line, MT-2. After coculture, the tumor necrosis factor-alpha (TNF-alpha) level in the medium was markedly elevated during the 7 days of culture, and MC3T3-E1 cells underwent apoptotic cell death. Marked apoptosis was also observed in MC3T3-E1 cells treated with MT-2 culture medium and in HTLV-I tax-expressing MC3T3-E1 clones, which both expressed high levels of TNF-alpha. This apoptosis was prevented by treatment with neutralizing anti-TNF-alpha antibody (alpha TNF). HTLV-I tax protein and TNF-alpha induced activation of NF-kappa B in apoptotic MC3T3-E1 cells. Decreased NF-kappa B activation was observed in HTLV-I tax-expressing MC3T3-E1 cells treated with alpha TNF. Our results suggest that HTLV-I tax activated NF-kappa B and subsequently TNF-alpha, leading to apoptosis of osteoblasts.
Kitajima
I
I
Department of Laboratory and Molecular Medicine, University of Kagoshima, Japan.
Nakajima
T
T
Imamura
T
T
Takasaki
I
I
Kawahara
K
K
Okano
T
T
Tokioka
T
T
Soejima
Y
Y
Abeyama
K
K
Maruyama
I
I
D000818:Animals; D000937:Antigen-Antibody Reactions; D017209:Apoptosis; D002999:Clone Cells; D018920:Coculture Techniques; D003470:Culture Media; D016207:Cytokines / Q000032:analysis; D016356:Gene Products, tax / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D003470:Culture Media; D016207:Cytokines; D016356:Gene Products, tax; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha