Peterson R L, Bozza M M, Dorner A J
Department of Preclinical Research and Development, Genetics Institute, Cambridge, Massachusetts, USA.
Am J Pathol. 1996 Sep;149(3):895-902.
Recombinant human (rh) interleukin (IL)-11 has been shown to reduce gastrointestinal mucosal injury after chemotherapy or irradiation in several animal models. As reduction of cellular proliferation can be cytoprotective, we have examined the effect of rhIL-11 compared with transforming growth factor (TGF)-beta 1 on the proliferation and cell cycle progression of a rat intestinal cell line, IEC-6. IEC-6 cells treated with rhIL-11 or rhTGF-beta 1 exhibited a reduced proliferative rate as measured by cell counts and [3H]thymidine incorporation. The presence of neutralizing anti-TGF-beta 1 antibodies did not block the antiproliferative effect of rhIL-11 indicating that the rhIL-11 activity was not mediated through the induction of endogenous TGF-beta 1 production. Growth inhibition correlated with delayed entry into S phase of the cell cycle. Cell cycle arrest was associated with suppression of retinoblastoma protein phosphorylation. Transient cell cycle arrest is a possible mechanism by which rhIL-11 may protect intestinal epithelial cells from damage induced by chemotherapy or radiation therapy. This study provides a rationale for the clinical use of rhIL-11 to preserve the integrity of the gastrointestinal mucosa during cancer treatment regimens.
在多个动物模型中，重组人（rh）白细胞介素（IL）-11已显示出可减轻化疗或放疗后胃肠道黏膜损伤。由于细胞增殖的减少具有细胞保护作用，我们已将rhIL-11与转化生长因子（TGF）-β1相比较，研究了其对大鼠肠细胞系IEC-6增殖和细胞周期进程的影响。用rhIL-11或rhTGF-β1处理的IEC-6细胞，通过细胞计数和[3H]胸苷掺入法测定，其增殖率降低。中和性抗TGF-β1抗体的存在并未阻断rhIL-11的抗增殖作用，这表明rhIL-11的活性不是通过诱导内源性TGF-β1的产生来介导的。生长抑制与细胞周期进入S期延迟相关。细胞周期停滞与视网膜母细胞瘤蛋白磷酸化的抑制有关。短暂的细胞周期停滞可能是rhIL-11保护肠上皮细胞免受化疗或放疗诱导损伤的一种机制。本研究为rhIL-11在癌症治疗方案中保护胃肠道黏膜完整性的临床应用提供了理论依据。
