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Induction of apoptosis in murine clonal osteoblasts expressed by human T‐cell leukemia virus type I tax by NF‐κPB and TNF‐α
Author(s) -
Kitajima Isao,
Nakajima Toshihiro,
Imamura Takeshi,
Takasaki Ikuko,
Kawahara Koichi,
Okano Toshihiro,
Tokioka Takeshi,
Soejima Yasuko,
Abeyama Kazuhiro,
Maruyama Ikuro
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650110209
Subject(s) - apoptosis , tumor necrosis factor alpha , microbiology and biotechnology , cell culture , nfkb1 , biology , cancer research , human t lymphotropic virus 1 , osteoblast , leukemia , immunology , in vitro , t cell leukemia , biochemistry , genetics , gene , transcription factor
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‐κB (NF‐κB). MC3T3‐E1 cells were cocultured with an irradiated HTLV‐I‐producing lymphocyte cell line, MT‐2. After coculture, the tumor necrosis factor‐α (TNF‐α) 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‐α. This apoptosis was prevented by treatment with neutralizing anti‐TNF‐α antibody (αTNF). HTLV‐I tax protein and TNF‐α induced activation of NF‐κB in apoptotic MC3T3‐E1 cells. Decreased NF‐κB activation was observed in HTLV‐I tax ‐expressing MC3T3‐E1 cells treated with αTNF. Our results suggest that HTLV‐I tax activated NF‐κB and subsequently TNF‐α, leading to apoptosis of osteoblasts.