Gómez-Benito Maria, Balsas Patricia, Bosque Alberto, Anel Alberto, Marzo Isabel, Naval Javier
Departamento de Bioquimica, Biologia Molecular y Cellular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain.
FEBS Lett. 2005 Nov 7;579(27):6217-22. doi: 10.1016/j.febslet.2005.10.007. Epub 2005 Oct 17.
Interferon-alpha (IFN-alpha) is currently used for the therapy of multiple myeloma (MM) though it is only effective in some patients. IFN-alpha induces apoptosis in some MM cell lines and it has been proposed to occur through an autocrine loop involving Apo2L/TRAIL. We have analysed the sensitivity to IFN-alpha and Apo2L/TRAIL of five MM cell lines and found no correlation between the apoptosis inducing ability of both cytokines. IFN-alpha-induced apoptosis in MM cells was not prevented by a caspase-8 selective inhibitor (Z-IETD-fmk) or blocking Apo2L/TRAIL. However, human monocytes treated with IFN-alpha release bioactive Apo2L/TRAIL to culture media which was cytotoxic for MM cells resistant to IFN-alpha. We propose that Apo2L/TRAIL released from IFN-alpha-stimulated blood monocytes would be a major mediator of the anti-myeloma effect of IFN-alpha in vivo.
α干扰素（IFN-α）目前用于治疗多发性骨髓瘤（MM），不过仅对部分患者有效。IFN-α可诱导某些MM细胞系发生凋亡，并且有人提出这是通过涉及Apo2L/TRAIL的自分泌环实现的。我们分析了5种MM细胞系对IFN-α和Apo2L/TRAIL的敏感性，发现这两种细胞因子的凋亡诱导能力之间没有相关性。MM细胞中IFN-α诱导的凋亡不受半胱天冬酶-8选择性抑制剂（Z-IETD-fmk）或阻断Apo2L/TRAIL的影响。然而，用IFN-α处理的人单核细胞会向培养基中释放具有生物活性的Apo2L/TRAIL，该物质对抵抗IFN-α的MM细胞具有细胞毒性。我们提出，从IFN-α刺激的血液单核细胞释放的Apo2L/TRAIL将是IFN-α在体内抗骨髓瘤作用的主要介质。
