Roth M, Nauck M, Tamm M, Perruchoud A P, Ziesche R, Block L H
Department of Internal Medicine and Research, University Hospital Basel, Switzerland.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1312-6. doi: 10.1073/pnas.92.5.1312.
The functional relevance of interleukin 6 (IL-6) in platelet-derived growth factor (PDGF)-induced cell growth was evaluated in cultures of human fibroblasts, vascular smooth muscle cells, and mesangial cells. The three isoforms of the PDGF--namely, PDGF-AA, -AB, and -BB--induced the expression of the IL-6 gene and proliferation of the nontransformed cells. PDGF-induced transcription, translation, and secretion of IL-6 were diminished in the presence of IL-6 antisense oligonucleotides. While neutralizing anti-IL-6 antibodies failed to affect the growth factor-dependent cell proliferation, IL-6 antisense oligonucleotides inhibited cell division. In addition, IL-6 antisense oligonucleotides abolished PDGF-induced transcription of the genes coding for the cell division cycle 2-related protein (CDC2) and proliferating cell nuclear antigen (PCNA), both of which are regulated in a cell cycle-dependent manner. It is concluded that PDGF-dependent proliferation of nontransformed cells involves the action of intracellular IL-6.
在人成纤维细胞、血管平滑肌细胞和系膜细胞培养物中评估了白细胞介素6（IL-6）在血小板衍生生长因子（PDGF）诱导的细胞生长中的功能相关性。PDGF的三种同工型，即PDGF-AA、-AB和-BB，诱导了IL-6基因的表达以及未转化细胞的增殖。在存在IL-6反义寡核苷酸的情况下，PDGF诱导的IL-6转录、翻译和分泌减少。虽然中和性抗IL-6抗体未能影响生长因子依赖性细胞增殖，但IL-6反义寡核苷酸抑制了细胞分裂。此外，IL-6反义寡核苷酸消除了PDGF诱导的编码细胞分裂周期2相关蛋白（CDC2）和增殖细胞核抗原（PCNA）的基因的转录，这两种蛋白均以细胞周期依赖性方式受到调节。得出的结论是，未转化细胞的PDGF依赖性增殖涉及细胞内IL-6的作用。
