Kitajima I, Nakajima T, Imamura T, Takasaki I, Kawahara K, Okano T, Tokioka T, Soejima Y, Abeyama K, Maruyama I
Department of Laboratory and Molecular Medicine, University of Kagoshima, Japan.
J Bone Miner Res. 1996 Feb;11(2):200-10. doi: 10.1002/jbmr.5650110209.
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.
我们在小鼠克隆成骨细胞MC3T3-E1细胞中，研究了在人I型嗜T细胞白血病病毒（HTLV-I）tax蛋白存在的情况下，各种细胞因子的作用。破骨细胞和成骨细胞介导的骨骼重塑由细胞因子协调，而细胞因子可被HTLV-I tax蛋白通过核因子κB（NF-κB）激活。将MC3T3-E1细胞与经辐照的产生HTLV-I的淋巴细胞系MT-2共培养。共培养后，培养基中的肿瘤坏死因子-α（TNF-α）水平在培养的7天内显著升高，并且MC3T3-E1细胞发生凋亡性细胞死亡。在用MT-2培养基处理的MC3T3-E1细胞以及表达HTLV-I tax的MC3T3-E1克隆中也观察到明显的凋亡，这两者均表达高水平的TNF-α。用中和抗TNF-α抗体（αTNF）处理可防止这种凋亡。HTLV-I tax蛋白和TNF-α在凋亡的MC3T3-E1细胞中诱导NF-κB的激活。在用αTNF处理的表达HTLV-I tax的MC3T3-E1细胞中观察到NF-κB激活减少。我们的结果表明，HTLV-I tax激活NF-κB，随后激活TNF-α，导致成骨细胞凋亡。
