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

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      Abstract

      OBJECTIVE: Our purpose was to learn whether cytokines such as interleukin-1β 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.
      STUDY DESIGN: Secondary cultures of human umbilical vein endothelial cells were grown to confluence and treated with interleukin-1β, 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-1β action was probed with interleukin-1β receptor antagonist and selected inhibitors.
      RESULTS: Interleukin-1β (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 sen at 0.23 ng/ml. Interleukin-1 receptor antagonist, cycloheximide, and actinomycin D blocked the effects of interleukin-1β (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-1β and interleukin-4 appeared to be specific, because a large series of related interleukins and other growth factors and cytokines were without effect.
      CONCLUSION: Interleukin-1β and interleukin-4 increase parathyroid hormone—related protein secretion in human umbilical vein endothelial cells in culture. Because interleukin-1β 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-1β endothelial action and secretion of the vasorelaxant parathyroid hormone—related peptide.

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      References

        • Martin TJ
        • Mosely JM
        • Gillespie MT
        Parathyroid hormone—related protein: biochemistry and molecular biology.
        Crit Rev Biochem Mol Biol. 1991; 26: 377-395
        • Orloff JJ
        • Wu TL
        • Stewart AF
        Parathyroid hormone-like proteins: biochemical responses and receptor interactions.
        Endocrinol Rev. 1989; 10: 476-495
        • Ikeda K
        • Weir EC
        • Mangin M
        • et al.
        Expression of messenger ribonucleic acids encoding a parathyroid hormone—like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas.
        Mol Endocrinol. 1988; 2: 1230-1236
        • Thiede MA
        • Rodan GA
        Expression of a calcium-mobilizing parathyroid hormone—like peptide in lactating mammary tissue.
        Science. 1988; 242: 278-280
        • Burton PBJ
        • Moniz C
        • Quirke P
        • et al.
        Parathyroid hormone—related peptide: expression in fetal and neonatal development.
        J Pathol. 1992; 167: 291-296
        • Broadus AE
        • Mangin M
        • Ikeda K
        • et al.
        Humoral hypercalcemia of cancer.
        N Engl J Med. 1988; 319: 556-563
        • de Papp AE
        • Stewart AF
        Parathyroid hormone—related protein: a peptide of diverse physiologic functions.
        Trends Endocrinol Metab. 1993; 4: 181-187
        • Shew RL
        • Yee JA
        • Kliewer DB
        • Keflemariam YJ
        • McNeill DL
        Parathyroid hormone—related protein inhibits stimulated uterine contraction in vitro.
        J Bone Miner Res. 1991; 6: 955-959
        • Winquist RJ
        • Baskin EF
        • Vlasuk GP
        Synthetic tumor-derived human hypercalcemic factor exhibits parathyroid hormone—like vasorelaxation in renal arteries.
        Biochem Biophys Res Commun. 1987; 149: 227-232
        • MacIsaac RJ
        • Horne RSC
        • Caple IW
        • Martin TJ
        • Wintour EM
        Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses.
        Am J Physiol. 1993; 264: E37-E44
      1. Ferguson JE II, Gorman J, Bruns DE, et al. Abundant expression of parathyroid hormone—related protein in human amnion and its association with labor. Proc Natl Acad Sci U S A 1992;89"8348-8.

        • Rian E
        • Jemtland R
        • Olstad OK
        • et al.
        Parathyroid hormone—related protein is produced by cultured endothelial cells: a possible role in angiogenesis.
        Biochem Biophys Res Commun. 1994; 198: 740-747
        • Ishikawa M
        • Ouchi Y
        • Akishita M
        • et al.
        Immunocytochemical detection of parathyroid hormone—related protein in vascular endothelial cells.
        Biochem Biophys Res Commun. 1994; 199: 547-551
        • Ferguson II, JE
        • Seaner R
        • Bruns DE
        • et al.
        Expression of parathyroid hormone—related protein and its receptor in human umbilical cord: evidence for a paracrine system involving umbilical vessels.
        Am J Obstet Gynecol. 1994; 170: 1018-1026
        • Funk JL
        • Krul EJT
        • Moser AH
        • et al.
        Endotoxin increases parathyroid hormone—related protein mRNA levels in mouse spleen.
        J Clin Invest. 1993; 92: 2546-2552
        • Cozzolino F
        • Torcia M
        • Aldinucci D
        • et al.
        Interleukin 1 is an autocrine regulator of human endothelial cell growth.
        in: Proc Natl Acad Sci U S A. 87. 1990: 6487-6491
        • Hongo T
        • Kupfer J
        • Enomota H
        • et al.
        Abundant expression of parathyroid hormone—related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation.
        J Clin Invest. 1991; 88: 1841-1847
        • Lowry OH
        • Rosebrough NF
        • Farr AI
        • Randle RJ
        Protein measurement with the Folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Broadus AE
        • Stewart AF
        Parathyroid hormone—related protein: structure, processing, and physiological actions.
        in: Bilezikian JP Levine MA Marcus R The parathyroids. Raven Press, New York1994: 259-294
        • Adachi N
        • Yamaguchi K
        • Miyake Y
        • et al.
        Parathyroid hormone—related protein as a possible autocrine growth inhibitor for lymphocytes.
        Biochem Biophys Res Commun. 1990; 166: 1088-1094
        • Funk JL
        • Shigenaga JK
        • Moser AH
        • et al.
        Cytokine regulation of parathyroid hormone—related protein messenger ribonucleic acid levels in mouse spleen: paradoxical effects of interferon-γ and interleukin-4.
        Endocrinology. 1994; 135: 351-358
        • Dinarello C
        Interleukin-1 and interleukin-1 antagonism.
        Blood. 1991; 77: 1627-1652
        • Kaiser J
        • Bickel CA
        • Bochner BS
        • Schleimer RP
        The effects of the potent glucocorticoid budesonide on adhesion of eosinophils to human vascular endothelial cells and on endothelial expression of adhesion molecules.
        J Pharmacol Exp Ther. 1993; 267: 245-259
        • Howells G
        • Pham P
        • Taylor D
        • Foxwell B
        • Feldman M
        Interleukin 4 induces interleukin 6 production by endothelial cells: synergy with interferon-gamma.
        Eur J Immunol. 1991; 21: 97-101
        • Hawrylowicz CM
        • Howells GL
        • Feldman M
        Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production.
        J Exp Med. 1991; 174: 785-790