日本的一个研究小组在新一期《自然—医学》杂志网络版上报告说,干扰素能控制作为血细胞源头的造血干细胞的作用,组合使用干扰素和抗癌剂或许能创造出一种效果好且副作用小的白血病治疗方法。
干扰素是一种广谱抗病毒剂,这种物质主要通过细胞表面受体作用使细胞产生抗病毒蛋白,从而抑制病毒复制。目前,干扰素常被用于治疗肝炎等病。
来自东京医科齿科大学和秋田大学的研究人员给实验鼠注入能令它们体内产生干扰素的物质,然后分析实验鼠造血干细胞的变化。他们发现,如果短时间注入这种物质,造血干细胞就会增殖,而一旦持续注入这种物质,实验鼠体内的造血干细胞又会减少。这表明,干扰素能够左右造血干细胞的作用。
在慢性骨髓性白血病患者体内,存在一种类似造血干细胞的白血病干细胞,这种干细胞能产生白血病细胞。用抗癌剂治疗白血病的时候,由于抗癌剂只对增殖中的细胞能充分发挥效用,而白血病干细胞又容易进入休眠状态,所以抗癌剂的效果常常不能完全发挥,这也是白血病容易复发的原因。
而上述新研究表明,短时间给予干扰素能激活造血干细胞。研究人员认为,可以利用这一机制,在实施抗癌剂治疗前,先用干扰素激活白血病干细胞,这样就有可能提高抗癌剂的效果。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Medicine 31 May 2009 | doi:10.1038/nm.1973
Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion
Taku Sato1,2, Nobuyuki Onai1,2, Hiroki Yoshihara3, Fumio Arai3, Toshio Suda3 & Toshiaki Ohteki1,2,4
Type I interferons (IFNs), a family of cytokines, orchestrate numerous biological and cellular processes1, 2, 3. Although it is well known that type I IFNs are essential for establishing the host antiviral state4, their role in hematopoietic homeostasis has not been studied. Here we show that type I IFNs induce proliferation and exhaustion in hematopoietic stem cells (HSCs) and that interferon regulatory factor-2 (IRF2), a transcriptional suppressor of type I IFN signaling5, 6, preserves the self-renewal and multilineage differentiation capacity of HSCs. HSCs were substantially less abundant in the bone marrow of Irf2-/- as compared to Irf2+/- mice. Irf2-/- HSCs showed enhanced cell cycling status and failed to produce hematopoietic cells in competitive repopulation assays, and the reconstituting capacity of Irf2-/- HSCs was restored by disabling type I IFN signaling in these cells. In wild-type mice, injection of poly(I:C), an inducer of type I IFN signaling, or IFN- induced HSC proliferation, and chronic type I IFN signaling further reduced the number of quiescent HSCs. Notably, combined poly(I:C) and 5-fluorouracil (5-FU) treatment allowed exogenous HSC engraftment and hematopoietic reconstitution in WT mice. Our findings provide insight into the molecular basis for the maintenance of HSC quiescence and may lead to improvements in bone marrow transplantation and type I IFN–based therapies for viral infection and cancer.
1 Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
2 Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.
3 Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Tokyo, Japan.
4 Department of Biodefense Research, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.