Imaizumi T, Itaya H, Nasu S, Yoshida H, Matsubara Y, Fujimoto K, Matsumiya T, Kimura H, Satoh K
Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, Japan.
Thromb Haemost. 2000 Jun;83(6):949-55.
Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells. We studied the production of VEGF by human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with interleukin-1alpha (IL-1alpha). HUVEC expressed VEGF mRNA in response to IL-1alpha in dose- and time-dependent manners. In HUVEC VEGF protein was detected only in cell lysates whereas in SMC most of the VEGF protein was detected in the conditioned medium. Immunofluorescent staining also confirmed the cell-associated VEGF in HUVEC. IL-1alpha also induced the expression of mRNA for IL-1alpha itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1alpha-induced expression of VEGF mRNA, and IL-1alpha may mediate, at least in part, VEGF expression in response to IL-1alpha. The growth of HUVEC stimulated with IL-1alpha was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1alpha and VEGF may play an important role in autocrine growth regulation of HUVEC.
血管内皮生长因子(VEGF)是一种针对内皮细胞的特异性促有丝分裂原。我们研究了人脐静脉内皮细胞(HUVEC)和平滑肌细胞(SMC)在白细胞介素-1α(IL-1α)刺激下VEGF的产生情况。HUVEC对IL-1α的刺激以剂量和时间依赖性方式表达VEGF mRNA。在HUVEC中,仅在细胞裂解物中检测到VEGF蛋白,而在SMC中,大部分VEGF蛋白在条件培养基中被检测到。免疫荧光染色也证实了HUVEC中与细胞相关的VEGF。IL-1α还诱导了HUVEC中IL-1α自身mRNA的表达。用环己酰亚胺处理HUVEC可轻微抑制IL-1α诱导的VEGF mRNA表达,并且IL-1α可能至少部分介导了对IL-1α应答的VEGF表达。抗VEGF中和抗体可抑制IL-1α刺激的HUVEC生长。我们得出结论,IL-1α和VEGF可能在HUVEC的自分泌生长调节中起重要作用。