Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Dec;78(6):1432–1438. doi: 10.1172/JCI112732

Inducible interleukin-1 gene expression in human vascular smooth muscle cells.

P Libby, J M Ordovas, L K Birinyi, K R Auger, C A Dinarello
PMCID: PMC423884  PMID: 3491091

Abstract

Interleukin-1 (IL-1) mediates many components of generalized host response to injury and may also contribute to local vascular pathology during immune or inflammatory responses. Because altered function of smooth muscle cells (SMC) accompanies certain vascular diseases, we tested whether SMC themselves might produce this hormone. Unstimulated SMC contain little or no IL-1 mRNA. However, exposure to bacterial endotoxin caused accumulation of IL-1 mRNA in SMC cultured from human vessels. Endotoxin maximally increased IL-1 beta mRNA in SMC after 4-6 h. The lowest effective concentration of endotoxin was 10 pg/ml. 10 ng/ml produced maximal increases in IL-1 beta mRNA. Interleukin-1 alpha mRNA was detected when SMC were incubated with endotoxin under "superinduction" conditions with cycloheximide. Endotoxin-stimulated SMC also released biologically functional IL-1, measured as thymocyte costimulation activity inhibitable by anti-IL-1 antibody. Thus, human SMC can express IL-1 beta and IL-1 alpha genes, or very similar ones, and secrete biologically active product in response to a pathological stimulus. Endogenous local production of this inflammatory mediator by the blood vessel wall's major cell type could play an important early role in the pathogenesis of vasculitis and arteriosclerosis.

Full text

PDF
1432

Images in this article

1433Image
on p.1433
1433Image
on p.1433
1434Image
on p.1434
1434Image
on p.1434
1434Image
on p.1434
1434Image
on p.1434
1434Image
on p.1434
1435Image
on p.1435
1435Image
on p.1435
1435Image
on p.1435

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albrightson C. R., Baenziger N. L., Needleman P. Exaggerated human vascular cell prostaglandin biosynthesis mediated by monocytes: role of monokines and interleukin 1. J Immunol. 1985 Sep;135(3):1872–1877. [PubMed] [Google Scholar]
  2. Auron P. E., Webb A. C., Rosenwasser L. J., Mucci S. F., Rich A., Wolff S. M., Dinarello C. A. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. doi: 10.1073/pnas.81.24.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bevilacqua M. P., Pober J. S., Majeau G. R., Fiers W., Cotran R. S., Gimbrone M. A., Jr Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4533–4537. doi: 10.1073/pnas.83.12.4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bond J. F., Farmer S. R. Regulation of tubulin and actin mRNA production in rat brain: expression of a new beta-tubulin mRNA with development. Mol Cell Biol. 1983 Aug;3(8):1333–1342. doi: 10.1128/mcb.3.8.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bywater M., Bywater R., Hellman L. A novel chromatographic procedure for purification of bacterial plasmids. Anal Biochem. 1983 Jul 1;132(1):219–224. doi: 10.1016/0003-2697(83)90451-7. [DOI] [PubMed] [Google Scholar]
  8. Colucci M., Balconi G., Lorenzet R., Pietra A., Locati D., Donati M. B., Semeraro N. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest. 1983 Jun;71(6):1893–1896. doi: 10.1172/JCI110945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dinarello C. A. An update on human interleukin-1: from molecular biology to clinical relevance. J Clin Immunol. 1985 Sep;5(5):287–297. doi: 10.1007/BF00918247. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A. Interleukin-1: amino acid sequences, multiple biological activities and comparison with tumor necrosis factor (cachectin). Year Immunol. 1986;2:68–89. [PubMed] [Google Scholar]
  11. Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
  12. Efrat S., Kaempfer R. Control of biologically active interleukin 2 messenger RNA formation in induced human lymphocytes. Proc Natl Acad Sci U S A. 1984 May;81(9):2601–2605. doi: 10.1073/pnas.81.9.2601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fontana A., Fierz W. The endothelium--astrocyte immune control system of the brain. Springer Semin Immunopathol. 1985;8(1-2):57–70. doi: 10.1007/BF00197247. [DOI] [PubMed] [Google Scholar]
  14. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  15. Harlan J. M. Leukocyte-endothelial interactions. Blood. 1985 Mar;65(3):513–525. [PubMed] [Google Scholar]
  16. Libby P., O'Brien K. V. Culture of quiescent arterial smooth muscle cells in a defined serum-free medium. J Cell Physiol. 1983 May;115(2):217–223. doi: 10.1002/jcp.1041150217. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Libby P., Wyler D. J., Janicka M. W., Dinarello C. A. Differential effects of human interleukin-1 on growth of human fibroblasts and vascular smooth muscle cells. Arteriosclerosis. 1985 Mar-Apr;5(2):186–191. doi: 10.1161/01.atv.5.2.186. [DOI] [PubMed] [Google Scholar]
  19. Maizel A. L., Lachman L. B. Control of human lymphocyte proliferation by soluble factors. Lab Invest. 1984 Apr;50(4):369–377. [PubMed] [Google Scholar]
  20. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  21. Matsushima K., Procopio A., Abe H., Scala G., Ortaldo J. R., Oppenheim J. J. Production of interleukin 1 activity by normal human peripheral blood B lymphocytes. J Immunol. 1985 Aug;135(2):1132–1136. [PubMed] [Google Scholar]
  22. Miossec P., Cavender D., Ziff M. Production of interleukin 1 by human endothelial cells. J Immunol. 1986 Apr 1;136(7):2486–2491. [PubMed] [Google Scholar]
  23. Montesano R., Orci L., Vassalli P. Human endothelial cell cultures: phenotypic modulation by leukocyte interleukins. J Cell Physiol. 1985 Mar;122(3):424–434. doi: 10.1002/jcp.1041220313. [DOI] [PubMed] [Google Scholar]
  24. Moyer C. F., Reinisch C. L. The role of vascular smooth muscle cells in experimental autoimmune vasculitis. I. The initiation of delayed type hypersensitivity angiitis. Am J Pathol. 1984 Dec;117(3):380–390. [PMC free article] [PubMed] [Google Scholar]
  25. Peach M. J., Loeb A. L., Singer H. A., Saye J. Endothelium-derived vascular relaxing factor. Hypertension. 1985 May-Jun;7(3 Pt 2):I94–100. doi: 10.1161/01.hyp.7.3_pt_2.i94. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Rosenwasser L. J., Dinarello C. A. Ability of human leukocytic pyrogen to enhance phytohemagglutinin induced murine thymocyte proliferation. Cell Immunol. 1981 Sep 1;63(1):134–142. doi: 10.1016/0008-8749(81)90034-4. [DOI] [PubMed] [Google Scholar]
  28. Ross R., Raines E., Bowen-Pope D. Growth factors from platelets, monocytes, and endothelium: their role in cell proliferation. Ann N Y Acad Sci. 1982 Dec 10;397:18–24. doi: 10.1111/j.1749-6632.1982.tb43413.x. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Sauder D. N. Epidermal cytokines: properties of epidermal cell thymocyte-activating factor (ETAF). Lymphokine Res. 1984 Summer;3(4):145–151. [PubMed] [Google Scholar]
  31. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  32. Stern D. M., Bank I., Nawroth P. P., Cassimeris J., Kisiel W., Fenton J. W., 2nd, Dinarello C., Chess L., Jaffe E. A. Self-regulation of procoagulant events on the endothelial cell surface. J Exp Med. 1985 Oct 1;162(4):1223–1235. doi: 10.1084/jem.162.4.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Unanue E. R., Kíely J. M. Synthesis and secretion of a mitogenic protein by macrophages: description of a superinduction phenomenon. J Immunol. 1977 Sep;119(3):925–931. [PubMed] [Google Scholar]
  34. Wagner C. R., Vetto R. M., Burger D. R. Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells. Cell Immunol. 1985 Jun;93(1):91–104. doi: 10.1016/0008-8749(85)90391-0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES