Department of Orthodontics and Dentofacial Orthopedics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Calcif Tissue Int. 2010 Mar;86(3):242-8. doi: 10.1007/s00223-010-9335-6. Epub 2010 Jan 29.
It has recently been reported that tumor necrosis factor (TNF)-alpha has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine interleukin (IL)-18 inhibits TNF-alpha-mediated osteoclastogenesis in mouse bone marrow cultures. In the present study, the effect of IL-18 on TNF-alpha-mediated osteoclastogenesis was investigated in vivo. We administered TNF-alpha with or without IL-18 into the supracalvaria of mice. The number of osteoclasts in the suture of the calvaria was increased in mice administered TNF-alpha. The number of osteoclasts in mice administered both TNF-alpha and IL-18 was lower than that in mice administered TNF-alpha alone. We previously showed that IL-12 and IL-18 synergistically inhibit TNF-alpha-mediated osteoclastogenesis in vitro. To assess the ability of these two cytokines to synergistically inhibit TNF-alpha-induced osteoclastogenesis in vivo, mice were administered the two cytokines at doses that did not inhibit osteoclast formation. The combination of IL-12 and IL-18 markedly inhibited TNF-alpha-induced osteoclastogenesis in vivo. To evaluate how IL-12 and IL-18 synergistically affect TNF-alpha-induced osteoclastogenesis, the IL-18 receptor (IL-18R) and IL-12R expression levels were analyzed by RT-PCR in bone marrow cells cultured with IL-12 or IL-18. IL-18R mRNA was increased in cells cultured with IL-12, while IL-12R mRNA was increased in cells cultured with IL-18. In addition, IL-18 inhibited TNF-alpha-induced osteoclastogenesis in mice with T-cell depletion caused by anti-CD4 and anti-CD8 antibodies. The present results suggest that IL-18 may inhibit TNF-alpha-mediated osteoclastogenesis in vivo via a T cell-independent mechanism.
最近有报道称肿瘤坏死因子 (TNF)-α 具有加速破骨细胞形成的能力。我们之前报道过促炎细胞因子白细胞介素 (IL)-18 可抑制小鼠骨髓培养物中 TNF-α 介导的破骨细胞形成。在本研究中，研究了 IL-18 对 TNF-α 介导的破骨细胞形成的体内影响。我们将 TNF-α 与 IL-18 一起或不一起注入小鼠的颅顶骨。给予 TNF-α 的小鼠颅缝中的破骨细胞数量增加。给予 TNF-α 和 IL-18 的小鼠中的破骨细胞数量低于仅给予 TNF-α 的小鼠。我们之前表明，IL-12 和 IL-18 协同抑制体外 TNF-α 介导的破骨细胞形成。为了评估这两种细胞因子在体内协同抑制 TNF-α 诱导的破骨细胞形成的能力，以不抑制破骨细胞形成的剂量给予两种细胞因子。IL-12 和 IL-18 的组合在体内显著抑制 TNF-α 诱导的破骨细胞形成。为了评估 IL-12 和 IL-18 如何协同影响 TNF-α 诱导的破骨细胞形成，通过 RT-PCR 分析了用 IL-12 或 IL-18 培养的骨髓细胞中的 IL-18 受体 (IL-18R) 和 IL-12R 表达水平。用 IL-12 培养的细胞中 IL-18R mRNA 增加，而用 IL-18 培养的细胞中 IL-12R mRNA 增加。此外，IL-18 抑制了由抗 CD4 和抗 CD8 抗体引起的 T 细胞耗竭的小鼠中 TNF-α 诱导的破骨细胞形成。本研究结果表明，IL-18 可能通过独立于 T 细胞的机制在体内抑制 TNF-α 介导的破骨细胞形成。
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