Interleukin-1 beta and interleukin-4 increase parathyroid hormone-related protein secretion by human umbilical vein endothelial cells in culture.

Abstract

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.