Cahir-McFarland E D, Davidson D M, Schauer S L, Duong J, Kieff E
The Channing Laboratory and Department of Infectious Diseases, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02130, USA.
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6055-60. doi: 10.1073/pnas.100119497.
Epstein-Barr virus (EBV) transforms B lymphocytes into lymphoblastoid cell lines usurping the Notch and tumor necrosis factor receptor pathways to effect transcription including NF-kappaB activation. To determine whether NF-kappaB activity is essential in the growth and survival of EBV-transformed lymphoblastoid cell lines, a nondegradable IkappaBalpha mutant was expressed under tetracycline regulation. Despite continued Bcl-2 and Bcl-x/L expression, NF-kappaB inhibition induced apoptosis as evidenced by poly(ADP-ribose) polymerase cleavage, nuclear condensation and fragmentation, and hypodiploid DNA content. Both caspase 3 and 8 activation and loss of mitochondrial membrane potential were observed in apoptotic cells. However, caspase inhibition failed to block apoptosis. These experiments indicate that NF-kappaB inhibitors may be useful in the therapy of EBV-induced cellular proliferation.
爱泼斯坦-巴尔病毒（EBV）通过利用Notch和肿瘤坏死因子受体途径来影响转录，包括激活核因子-κB（NF-κB），从而将B淋巴细胞转化为淋巴母细胞系。为了确定NF-κB活性在EBV转化的淋巴母细胞系的生长和存活中是否至关重要，在四环素调控下表达了一种不可降解的IκBα突变体。尽管Bcl-2和Bcl-x/L持续表达，但NF-κB抑制仍诱导了细胞凋亡，这通过聚（ADP-核糖）聚合酶裂解、核浓缩和碎片化以及亚二倍体DNA含量得以证明。在凋亡细胞中观察到了半胱天冬酶3和8的激活以及线粒体膜电位的丧失。然而，半胱天冬酶抑制未能阻止细胞凋亡。这些实验表明，NF-κB抑制剂可能对EBV诱导的细胞增殖治疗有用。
