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Thromb Haemost 2000; 83(06): 949-955
DOI: 10.1055/s-0037-1613948
Commentary
Schattauer GmbH

Expression of Vascular Endothelial Growth Factor in Human Umbilical Vein Endothelial Cells Stimulated with Interleukin-1α

An Autocrine Regulation of Angiogenesis and Inflammatory Reactions
Tadaatsu Imaizumi
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
,
Hiroyuki Itaya
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
,
Satoki Nasu
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
,
Hidemi Yoshida
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
,
Yuki Matsubara
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
,
Koji Fujimoto
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
,
Tomoh Matsumiya
1   Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Hiroto Kimura
1   Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Kei Satoh
2   From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki, Japan
› Author Affiliations
Further Information

Publication History

Received 22 March 1999

Accepted after resubmission 28 January 2000

Publication Date:
14 December 2017 (online)

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Summary

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-1α (IL-1α). HUVEC expressed VEGF mRNA in response to IL-1α in doseand 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-1α also induced the expression of mRNA for IL-1α itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1α-induced expression of VEGF mRNA, and IL-1α may mediate, at least in part, VEGF expression in response to IL-1α. The growth of HUVEC stimulated with IL-1α was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1α and VEGF may play an important role in autocrine growth regulation of HUVEC.

Key words

Vascular endothelial growth factor (VEGF) - endothelial cells - interleukin-1α - hypoxia - smooth muscle cells
 

  • References

  • 1 Leung DW, Cachianes G, Kuang W-J, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246: 1306-9.
    CrossrefPubMedGoogle Scholar
  • 2 Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989; 246: 1309-12.
    CrossrefPubMedGoogle Scholar
  • 3 Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993; 362: 841-4.
    CrossrefPubMedGoogle Scholar
  • 4 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 01: 27-31.
    CrossrefPubMedGoogle Scholar
  • 5 Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331: 1480-7.
    CrossrefPubMedGoogle Scholar
  • 6 Ramos MA, Kuzuya M, Esaki T, Miura S, Satake S, Asai T, Kanda S, Hayashi T, Iguchi A. Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 1998; 18: 1188-96.
    CrossrefPubMedGoogle Scholar
  • 7 Pertovaara L, Kaipainen A, Mustonen T, Orpana A, Ferrara N, Saksela O, Alitalo K. Vascular endothelial growth factor is induced in response to transforming growth factor- β in fibroblastic and epithelial cells. J Biol Chem 1994; 269: 6721-4.
    PubMedGoogle Scholar
  • 8 Li J, Perrella MA, Tsai J-C, Yet S-F, Hsieh C-M, Yoshizumi M, Patterson C, Endege WO, Zhou F, Lee M-E. Induction of vascular endothelial growth factor gene expression by interleukin-1β in rat aortic smooth muscle cells. J Biol Chem 1995; 270: 308-12.
    CrossrefPubMedGoogle Scholar
  • 9 Brogi E, Wu T, Namiki A, Isner JM. Indirect angiogenic cytokines upregulate VEGF and and bFGF gene expression in vascular smooth muscle cell, whereas hypoxia upregulates VEGF expression only. Circulation 1994; 90: 649-52.
    CrossrefPubMedGoogle Scholar
  • 10 Namiki A, Brogi E, Kearney M, Kim EA, Wu TG, Couffinhal T, Varticovski L, Isner JM. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J Biol Chem 1995; 270: 31189-95.
    CrossrefPubMedGoogle Scholar
  • 11 Maniscalco WM, Watkins RH, Finkelstein JN, Campbell MH. Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury. Am J Respir Cell Mol Biol 1995; 13: 377-86.
    CrossrefPubMedGoogle Scholar
  • 12 Gaudry M, Brégerie P, Andrieu V, El Benna J, Pocidalo M-A, Hakim J. Intracellular pool of vascular endothelial growth factor in human neutrophils. Blood 1997; 90: 4153-61.
    PubMedGoogle Scholar
  • 13 McLaren J, Prentice A, Charnock-Jones DS, Millican SA, Muller KH, Sharkey AM, Smith SK. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest 1996; 98: 482-9.
    CrossrefPubMedGoogle Scholar
  • 14 Neufeld G, Tessler S, Gitay-Goren H, Cohen T, Levi B-Z. Vascular endothelial growth factor and its receptors. Prog Growth Factor Res 1994; 05: 89-97.
    CrossrefPubMedGoogle Scholar
  • 15 Stone J, Itin A, Alon T, Pe’er J, Gnessin H, Chan-Ling T, Keshet E. Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 1995; 15: 4738-47.
    CrossrefPubMedGoogle Scholar
  • 16 Nomura M, Yamagishi S, Harada S, Hayashi Y, Yamashima T, Yamashita J, Yamamoto H. Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem 1995; 270: 28316-24.
    CrossrefPubMedGoogle Scholar
  • 17 Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992; 267: 26031-7.
    PubMedGoogle Scholar
  • 18 Park JE, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subenpithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 1993; 04: 1317-26.
    CrossrefPubMedGoogle Scholar
  • 19 Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992; 267: 10931-4.
    CrossrefPubMedGoogle Scholar
  • 20 Hayashi T, Abe K, Itoyama Y. Reduction of ischemic damage by application of vascular endothelial growth factor in rat brain after transient ischemia. J Cereb Blood Flow Metab 1998; 18: 887-95.
    CrossrefPubMedGoogle Scholar
  • 21 Tsurumi Y, Kearney M, Chen D, Silver M, Takeshita S, Yang J, Symes JF, Isner JM. Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. Circulation 1997; 96 (Suppl. II): 382-8.
    PubMedGoogle Scholar
  • 22 Hopkins SP, Bulgrin JP, Sims RL, Bowman B, Donovan DL, Schmidt SP. Controlled delivery of vascular endothelial growth factor promotes neovascularization and maintains limb function in a rabbit model of ischemia. J Vasc Surg 1998; 27: 886-94.
    CrossrefPubMedGoogle Scholar
  • 23 An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM. Stabilization of wild-type p53 by hypoxia-inducible factor 1a. Nature 1998; 392: 405-8.
    CrossrefPubMedGoogle Scholar
  • 24 Dejana E, Breviario F, Erroi A, Bussolino F, Mussoni L, Gramse M, Pintucci G, Casali B, Dinarello CA, Van Damme J, Mantovani A. Modulation of endothelial cell functions by different molecular species of interleukin 1. Blood 1987; 69: 695-9.
    PubMedGoogle Scholar
  • 25 Rossi V, Breviario F, Ghezzi P, Dejana E, Mantovani A. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science 1985; 229: 174-6.
    CrossrefPubMedGoogle Scholar
  • 26 Emeis JJ, Kooistra T. Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J Exp Med 1986; 163: 1260-6.
    CrossrefPubMedGoogle Scholar
  • 27 Zimmerman GA, Whatley RE, McIntyre TM, Benson DE, Prescott SM. Endothelial cells for studies of platelet-activating factor and arachidonate metabolites. Methods Enzymol 1990; 187: 520-35.
    PubMedGoogle Scholar
  • 28 Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol 1971; 50: 172-86.
    CrossrefPubMedGoogle Scholar
  • 29 Koyama M, Satoh K, Yoshida H, Suzuki S, Koie H, Takamatsu S. Surface coverage of vascular grafts with cultured human endothelial cells from subcutaneous fat tissue obtained with a biopsy needle. Thromb Haemost 1996; 76: 610-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Sato Y, Rifkin DB. Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis. J Cell Biol 1988; 107: 1199-205.
    CrossrefPubMedGoogle Scholar
  • 31 Dustin ML, Springer TA. Lymphocyte function associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 1988; 107: 321-31.
    CrossrefPubMedGoogle Scholar
  • 32 Majewska E, Paleolog E, Baj Z, Kralisz U, Feldmann M, Tchorzewski H. Role of tyrosine kinase enzymes in TNF-α and IL-1α induced expression of ICAM-1 and VCAM-1 on human umbilical vein endothelial cells. Scand J Immunol 1997; 45: 385-92.
    CrossrefPubMedGoogle Scholar
  • 33 Shingu M, Nobunaga M, Ezaki I, Yoshioka K. Recombinant human IL-1β and TNF-α stimulate production of IL-1α and IL-1β by vascular smooth muscle cells and IL-1α by vascular endothelial cells. Life Sci 1991; 49: 241-6.
    CrossrefPubMedGoogle Scholar
  • 34 Raines EW, Dower SK, Ross R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 1989; 243: 393-6.
    CrossrefPubMedGoogle Scholar
  • 35 Norrby K. Interleukin-1-α and de novo mammalian angiogenesis. Microvasc Res 1997; 54: 58-64.
    CrossrefPubMedGoogle Scholar
  • 36 Levy NS, Chung S, Furneaux H, Levy AP. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem 1998; 273: 6417-23.
    CrossrefPubMedGoogle Scholar
  • 37 Ben-Av P, Crofford LJ, Wilder RL, Hla T. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism of inflammatory angiogenesis. FEBS Lett 1995; 372: 83-7.
    CrossrefPubMedGoogle Scholar
  • 38 Newton R, Hart LA, Stevens DA, Bergmann M, Donnelly LE, Adcock IM, Barnes PJ. Effect of dexamethasone on interleukin-1β-(IL-1β)-induced nuclear factor-κB (NF-κB) and κB-dependent transcription in epithelial cells. Eur J Biochem 1998; 254: 81-9.
    CrossrefPubMedGoogle Scholar
  • 39 Adkins KK, Levan TD, Miesfeld RL, Bloom JW. Glucocorticoid regulation of GM-CSF: evidence for transcriptional mechanisms in airway epithelial cells. Am J Physiol 1998; 275: L372-8.
    PubMedGoogle Scholar
  • 40 Moriset S, Patry C, Lora M, de Brum-Fernandes AJ. Regulation of cyclooxygenase-2 expression in bovine chondrocytes in culture by interleukin-1α, tumor necrosis factor-α, glucocorticoids, and 17β-estradiol. J Rheumatol 1998; 25: 1146-53.
    PubMedGoogle Scholar
  • 41 Nauck M, Roth M, Tamm M, Eickelberg O, Wieland H, Stulz P, Perruchoud AP. Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids. Am J Respir Cell Mol Biol 1997; 16: 398-406.
    CrossrefPubMedGoogle Scholar
  • 42 Nauck M, Karakiulakis G, Perruchoud AP, Papakonstantinou E, Roth M. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human smooth muscle cells. Eur J Pharmacol 1998; 341: 309-15.
    CrossrefPubMedGoogle Scholar
  • 43 Harada S, Nagy JA, Sullivan KA, Thomas KA, Endo N, Rodan GA, Rodan SB. Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. J Clin Invest 1994; 93: 2490-6.
    CrossrefPubMedGoogle Scholar