Abstract
The authors have investigated the effects of cytokines and lipopolysaccharide (LPS) on mRNA levels of c-sis (platelet-derived growth factor (PDGF)-B chain), PDGF-A chain, and interleukin 1 beta (IL-1 beta) genes in human vascular endothelial cells (EC). IL-1, tumor necrosis factor (TNF), and LPS not only enhanced the accumulation of c-sis mRNA, but also induced IL-1 beta gene expression. Interferon-gamma (IFN-gamma), in contrast, suppressed the accumulation of c-sis mRNA profoundly and PDGF-A chain mRNA to a lesser extent. The cytokine, in addition, suppressed the release of PDGF-like proteins by EC, while maintaining the growth of EC. IFN-gamma, however, augmented the levels of IL-1 beta mRNA in cultured EC in association with LPS or IL-1, suggesting that the suppression of c-sis expression was not mediated through modulation of IL-1 gene expression by IFN-gamma. These results raise the possibility that IFN-gamma may play a novel regulatory role in the pathogenesis of vascular diseases such as atherosclerosis and vasculitis.
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- Barrett T. B., Benditt E. P. sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1099–1103. doi: 10.1073/pnas.84.4.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrett T. B., Gajdusek C. M., Schwartz S. M., McDougall J. K., Benditt E. P. Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6772–6774. doi: 10.1073/pnas.81.21.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
- Bevilacqua M. P., Pober J. S., Majeau G. R., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med. 1984 Aug 1;160(2):618–623. doi: 10.1084/jem.160.2.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cavender D. E., Haskard D. O., Joseph B., Ziff M. Interleukin 1 increases the binding of human B and T lymphocytes to endothelial cell monolayers. J Immunol. 1986 Jan;136(1):203–207. [PubMed] [Google Scholar]
- Collins T., Pober J. S., Gimbrone M. A., Jr, Hammacher A., Betsholtz C., Westermark B., Heldin C. H. Cultured human endothelial cells express platelet-derived growth factor A chain. Am J Pathol. 1987 Jan;126(1):7–12. [PMC free article] [PubMed] [Google Scholar]
- Daniel T. O., Gibbs V. C., Milfay D. F., Williams L. T. Agents that increase cAMP accumulation block endothelial c-sis induction by thrombin and transforming growth factor-beta. J Biol Chem. 1987 Sep 5;262(25):11893–11896. [PubMed] [Google Scholar]
- DiCorleto P. E., Bowen-Pope D. F. Cultured endothelial cells produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1919–1923. doi: 10.1073/pnas.80.7.1919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox P. L., DiCorleto P. E. Modified low density lipoproteins suppress production of a platelet-derived growth factor-like protein by cultured endothelial cells. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4774–4778. doi: 10.1073/pnas.83.13.4774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox P. L., DiCorleto P. E. Regulation of production of a platelet-derived growth factor-like protein by cultured bovine aortic endothelial cells. J Cell Physiol. 1984 Nov;121(2):298–308. doi: 10.1002/jcp.1041210206. [DOI] [PubMed] [Google Scholar]
- Friedman R. M., Vogel S. N. Interferons with special emphasis on the immune system. Adv Immunol. 1983;34:97–140. doi: 10.1016/s0065-2776(08)60378-8. [DOI] [PubMed] [Google Scholar]
- Friesel R., Komoriya A., Maciag T. Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol. 1987 Mar;104(3):689–696. doi: 10.1083/jcb.104.3.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gajdusek C., Carbon S., Ross R., Nawroth P., Stern D. Activation of coagulation releases endothelial cell mitogens. J Cell Biol. 1986 Aug;103(2):419–428. doi: 10.1083/jcb.103.2.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hajjar K. A., Hajjar D. P., Silverstein R. L., Nachman R. L. Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells. J Exp Med. 1987 Jul 1;166(1):235–245. doi: 10.1084/jem.166.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harlan J. M., Thompson P. J., Ross R. R., Bowen-Pope D. F. Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells. J Cell Biol. 1986 Sep;103(3):1129–1133. doi: 10.1083/jcb.103.3.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaye M., McConathy E., Drohan W., Tong B., Deuel T., Maciag T. Modulation of the sis gene transcript during endothelial cell differentiation in vitro. Science. 1985 May 17;228(4701):882–885. doi: 10.1126/science.3890179. [DOI] [PubMed] [Google Scholar]
- Knudsen P. J., Dinarello C. A., Strom T. B. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J Immunol. 1986 Nov 15;137(10):3189–3194. [PubMed] [Google Scholar]
- Kuo P. T., Wilson A. C., Goldstein R. C., Schaub R. G. Suppression of experimental atherosclerosis in rabbits by interferon-inducing agents. J Am Coll Cardiol. 1984 Jan;3(1):129–134. doi: 10.1016/s0735-1097(84)80438-6. [DOI] [PubMed] [Google Scholar]
- Leung D. Y., Geha R. S., Newburger J. W., Burns J. C., Fiers W., Lapierre L. A., Pober J. S. Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. J Exp Med. 1986 Dec 1;164(6):1958–1972. doi: 10.1084/jem.164.6.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Libby P., Ordovas J. M., Auger K. R., Robbins A. H., Birinyi L. K., Dinarello C. A. Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol. 1986 Aug;124(2):179–185. [PMC free article] [PubMed] [Google Scholar]
- Martinet Y., Bitterman P. B., Mornex J. F., Grotendorst G. R., Martin G. R., Crystal R. G. Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature. 1986 Jan 9;319(6049):158–160. doi: 10.1038/319158a0. [DOI] [PubMed] [Google Scholar]
- Matsubara T., Ziff M. Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium. Immunoelectron microscopic and electron microscopic morphometric analysis. Arthritis Rheum. 1987 Jan;30(1):18–30. doi: 10.1002/art.1780300103. [DOI] [PubMed] [Google Scholar]
- McIntyre T. M., Zimmerman G. A., Satoh K., Prescott S. M. Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate. J Clin Invest. 1985 Jul;76(1):271–280. doi: 10.1172/JCI111957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miossec P., Ziff M. Immune interferon enhances the production of interleukin 1 by human endothelial cells stimulated with lipopolysaccharide. J Immunol. 1986 Nov 1;137(9):2848–2852. [PubMed] [Google Scholar]
- Nachman R. L., Hajjar K. A., Silverstein R. L., Dinarello C. A. Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. J Exp Med. 1986 Jun 1;163(6):1595–1600. doi: 10.1084/jem.163.6.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nilsson J. Growth factors and the pathogenesis of atherosclerosis. Atherosclerosis. 1986 Dec;62(3):185–199. doi: 10.1016/0021-9150(86)90093-6. [DOI] [PubMed] [Google Scholar]
- Okada M., Yoshimura N., Ichimori Y., Kishimoto S., Nakai S., Nishino N., Kishimoto T. Immunologic and molecular characterizations of T cell-derived T cell activating factor. J Immunol. 1986 Feb 15;136(4):1288–1294. [PubMed] [Google Scholar]
- Pober J. S., Bevilacqua M. P., Mendrick D. L., Lapierre L. A., Fiers W., Gimbrone M. A., Jr Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol. 1986 Mar 1;136(5):1680–1687. [PubMed] [Google Scholar]
- Pober J. S., Gimbrone M. A., Jr, Cotran R. S., Reiss C. S., Burakoff S. J., Fiers W., Ault K. A. Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon. J Exp Med. 1983 Apr 1;157(4):1339–1353. doi: 10.1084/jem.157.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pohlman T. H., Stanness K. A., Beatty P. G., Ochs H. D., Harlan J. M. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol. 1986 Jun 15;136(12):4548–4553. [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Robbins K. C., Devare S. G., Aaronson S. A. Molecular cloning of integrated simian sarcoma virus: genome organization of infectious DNA clones. Proc Natl Acad Sci U S A. 1981 May;78(5):2918–2922. doi: 10.1073/pnas.78.5.2918. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
- Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
- Rossi V., Breviario F., Ghezzi P., Dejana E., Mantovani A. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science. 1985 Jul 12;229(4709):174–176. doi: 10.1126/science.2409598. [DOI] [PubMed] [Google Scholar]
- Shimokado K., Raines E. W., Madtes D. K., Barrett T. B., Benditt E. P., Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985 Nov;43(1):277–286. doi: 10.1016/0092-8674(85)90033-9. [DOI] [PubMed] [Google Scholar]
- Sitaras N. M., Sariban E., Pantazis P., Zetter B., Antoniades H. N. Human iliac artery endothelial cells express both genes encoding the chains of platelet-derived growth factor (PDGF) and synthesize PDGF-like mitogen. J Cell Physiol. 1987 Aug;132(2):376–380. doi: 10.1002/jcp.1041320228. [DOI] [PubMed] [Google Scholar]
- Stolpen A. H., Guinan E. C., Fiers W., Pober J. S. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol. 1986 Apr;123(1):16–24. [PMC free article] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tokunaga K., Taniguchi H., Yoda K., Shimizu M., Sakiyama S. Nucleotide sequence of a full-length cDNA for mouse cytoskeletal beta-actin mRNA. Nucleic Acids Res. 1986 Mar 25;14(6):2829–2829. doi: 10.1093/nar/14.6.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tovey M. G., Rochette-Egly C., Castagna M. Effect of interferon on concentrations of cyclic nucleotides in cultured cells. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3890–3893. doi: 10.1073/pnas.76.8.3890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tzeng D. Y., Deuel T. F., Huang J. S., Baehner R. L. Platelet-derived growth factor promotes human peripheral monocyte activation. Blood. 1985 Jul;66(1):179–183. [PubMed] [Google Scholar]
- Tzeng D. Y., Deuel T. F., Huang J. S., Senior R. M., Boxer L. A., Baehner R. L. Platelet-derived growth factor promotes polymorphonuclear leukocyte activation. Blood. 1984 Nov;64(5):1123–1128. [PubMed] [Google Scholar]
- Warner S. J., Auger K. R., Libby P. Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells. J Immunol. 1987 Sep 15;139(6):1911–1917. [PubMed] [Google Scholar]
- Young R. H., Mark G. J. Pulmonary vascular changes in scleroderma. Am J Med. 1978 Jun;64(6):998–1004. doi: 10.1016/0002-9343(78)90455-2. [DOI] [PubMed] [Google Scholar]
- Yu C. L., Haskard D. O., Cavender D., Johnson A. R., Ziff M. Human gamma interferon increases the binding of T lymphocytes to endothelial cells. Clin Exp Immunol. 1985 Dec;62(3):554–560. [PMC free article] [PubMed] [Google Scholar]





