Ferguson J E, Seaner R M, Bruns D E, Bruns M E
Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, USA.
Am J Obstet Gynecol. 1995 Aug;173(2):448-55; discussion 455-6. doi: 10.1016/0002-9378(95)90265-1.
Our purpose was to learn whether cytokines such as interleukin-1 beta and related (or antagonistic) cytokines, hormones, and growth factors could regulate secretion of the vasorelaxant parathyroid hormone-related protein in human umbilical vein endothelial cells in culture.
Secondary cultures of human umbilical vein endothelial cells were grown to confluence and treated with interleukin-1 beta, an array of factors with possible regulatory actions (cytokines, growth factors, vasoactive peptides, and steroids), and a phorbol ester as a stimulatory control. After 24 hours immunoreactive parathyroid hormone-related peptide in the media was measured by a two-site sandwich radioimmunoassay. The mechanism of interleukin-1 beta action was probed with interleukin-1 beta receptor antagonist and selected inhibitors.
Interleukin-1 beta (10 ng/ml) produced up to an eightfold increase in parathyroid hormone-related peptide secretion from human umbilical vein endothelial cells in culture (p < 0.01). Half-maximal stimulation was seen at 0.23 ng/ml. Interleukin-1 receptor antagonist, cycloheximide, and actinomycin D blocked the effects of interleukin-1 beta (p < 0.05). Interleukin-4 at 10 ng/ml and phorbol 12-myristate 13-acetate at 10(-7) mol/L significantly increased the secretion of parathyroid hormone-related peptide by human umbilical vein endothelial cells (p < 0.05). The time course of each interleukin showed an effect beyond 12 hours. The effects of interleukin-1 beta and interleukin-4 appeared to be specific, because a large series of related interleukins and other growth factors and cytokines were without effect.
Interleukin-1 beta and interleukin-4 increase parathyroid hormone-related protein secretion in human umbilical vein endothelial cells in culture. Because interleukin-1 beta messenger ribonucleic acid has been found in umbilical cord endothelial cells, we propose that the umbilical cord has a novel vasorelaxant regulatory system that uses interleukin-1 beta endothelial action and secretion of the vasorelaxant parathyroid hormone-related peptide.
我们的目的是了解诸如白细胞介素-1β以及相关（或拮抗）细胞因子、激素和生长因子等细胞因子是否能够调节培养的人脐静脉内皮细胞中血管舒张性甲状旁腺激素相关蛋白的分泌。
将人脐静脉内皮细胞的传代培养物培养至汇合状态，并用白细胞介素-1β、一系列具有可能调节作用的因子（细胞因子、生长因子、血管活性肽和类固醇）以及佛波酯作为刺激对照进行处理。24小时后，通过双位点夹心放射免疫测定法测量培养基中免疫反应性甲状旁腺激素相关肽。用白细胞介素-1β受体拮抗剂和选定的抑制剂探究白细胞介素-1β的作用机制。
白细胞介素-1β（10纳克/毫升）使培养的人脐静脉内皮细胞中甲状旁腺激素相关肽的分泌增加高达八倍（p < 0.01）。在0.23纳克/毫升时可见半数最大刺激。白细胞介素-1受体拮抗剂、放线菌酮和放线菌素D阻断了白细胞介素-1β的作用（p < 0.05）。10纳克/毫升的白细胞介素-4和10⁻⁷摩尔/升的佛波醇12 - 肉豆蔻酸酯13 - 乙酸盐显著增加了人脐静脉内皮细胞中甲状旁腺激素相关肽的分泌（p < 0.05）。每种白细胞介素的时间进程显示在12小时后有作用。白细胞介素-1β和白细胞介素-4的作用似乎具有特异性，因为一系列相关的白细胞介素以及其他生长因子和细胞因子均无作用。
白细胞介素-1β和白细胞介素-4增加培养的人脐静脉内皮细胞中甲状旁腺激素相关蛋白的分泌。由于在脐带内皮细胞中发现了白细胞介素-1β信使核糖核酸，我们提出脐带具有一种新的血管舒张调节系统，该系统利用白细胞介素-1β的内皮作用和血管舒张性甲状旁腺激素相关肽的分泌。
