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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ferguson
J E
JE
Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, USA.
Seaner
R M
RM
Bruns
D E
DE
Bruns
M E
ME
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism*
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D003609:Dactinomycin; D015847:Interleukin-4; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate