Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Nov;94(5):1864–1871. doi: 10.1172/JCI117536

Effect of gold sodium thiomalate and its thiomalate component on the in vitro expression of endothelial cell adhesion molecules.

P M Newman 1, S S To 1, B G Robinson 1, V J Hyland 1, L Schrieber 1
PMCID: PMC294592  PMID: 7525650

Abstract

Endothelial adhesion molecules play an important role in the tissue recruitment of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have investigated the effect of the antirheumatic drug gold sodium thiomalate on adhesion molecule protein and mRNA expression in cultured human endothelial cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated expression of vascular cell adhesion molecule-1 and E-selectin but not intercellular adhesion molecule-1 on endothelial cells. Gold sodium thiomalate also suppressed TNF-stimulated increases in vascular cell adhesion molecule-1 and E-selectin mRNA levels but had no effect on intercellular adhesion molecule-1 mRNA. Thiomalate (mercaptosuccinate), but not gold thioglucose or D-penicillamine, mimics the effect of gold sodium thiomalate at equimolar concentrations. We propose that the inhibition of vascular cell adhesion molecule-1 and E-selectin expression by gold sodium thiomalate is due to its thiomalate and not its gold component. Gold sodium thiomalate has a direct effect on endothelial adhesion molecule expression, and this may contribute to its antiinflammatory activity.

Full text

PDF
1864

Images in this article

Selected References

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

  1. Aguilera J. A., Newton G. L., Fahey R. C., Ward J. F. Thiol uptake by Chinese hamster V79 cells and aerobic radioprotection as a function of the net charge on the thiol. Radiat Res. 1992 May;130(2):194–204. [PubMed] [Google Scholar]
  2. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  3. Champion G. D., Graham G. G., Ziegler J. B. The gold complexes. Baillieres Clin Rheumatol. 1990 Dec;4(3):491–534. doi: 10.1016/s0950-3579(05)80005-6. [DOI] [PubMed] [Google Scholar]
  4. Chaudiere J., Wilhelmsen E. C., Tappel A. L. Mechanism of selenium-glutathione peroxidase and its inhibition by mercaptocarboxylic acids and other mercaptans. J Biol Chem. 1984 Jan 25;259(2):1043–1050. [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Corkill M. M., Kirkham B. W., Haskard D. O., Barbatis C., Gibson T., Panayi G. S. Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1. J Rheumatol. 1991 Oct;18(10):1453–1460. [PubMed] [Google Scholar]
  7. Cronstein B. N., Kimmel S. C., Levin R. I., Martiniuk F., Weissmann G. A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):9991–9995. doi: 10.1073/pnas.89.21.9991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cronstein B. N., Weissmann G. The adhesion molecules of inflammation. Arthritis Rheum. 1993 Feb;36(2):147–157. doi: 10.1002/art.1780360204. [DOI] [PubMed] [Google Scholar]
  9. Harth M., Keown P. A., Orange J. F. Monocyte dependent excited oxygen radical generation in rheumatoid arthritis: inhibition by gold sodium thiomalate. J Rheumatol. 1983 Oct;10(5):701–707. [PubMed] [Google Scholar]
  10. Harth M. Mechanisms of action of disease modifying antirheumatic drugs. J Rheumatol Suppl. 1992 Jan;32:100–103. [PubMed] [Google Scholar]
  11. Hopkins S. J., Meager A. Cytokines in synovial fluid: II. The presence of tumour necrosis factor and interferon. Clin Exp Immunol. 1988 Jul;73(1):88–92. [PMC free article] [PubMed] [Google Scholar]
  12. Jellum E., Munthe E. Fate of the thiomalate part after intramuscular administration of aurothiomalate in rheumatoid arthritis. Ann Rheum Dis. 1982 Aug;41(4):431–432. doi: 10.1136/ard.41.4.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jellum E., Munthe E., Guldal G., Aaseth J. Fate of the gold and the thiomalate part after intramuscular administration of aurothiomalate to mice. Ann Rheum Dis. 1980 Apr;39(2):155–158. doi: 10.1136/ard.39.2.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson B. A., Haines G. K., Harlow L. A., Koch A. E. Adhesion molecule expression in human synovial tissue. Arthritis Rheum. 1993 Feb;36(2):137–146. doi: 10.1002/art.1780360203. [DOI] [PubMed] [Google Scholar]
  15. Jornot L., Junod A. F. Variable glutathione levels and expression of antioxidant enzymes in human endothelial cells. Am J Physiol. 1993 May;264(5 Pt 1):L482–L489. doi: 10.1152/ajplung.1993.264.5.L482. [DOI] [PubMed] [Google Scholar]
  16. Kawakami A., Eguchi K., Migita K., Nakao H., Otsubo T., Ueki Y., Shimomura C., Tezuka H., Matsunaga M., Ishimaru T. Inhibitory effects of gold sodium thiomalate on the proliferation and interferon-gamma induced HLA-DR expression in human endothelial cells. J Rheumatol. 1990 Apr;17(4):430–435. [PubMed] [Google Scholar]
  17. Koch A. E., Burrows J. C., Haines G. K., Carlos T. M., Harlan J. M., Leibovich S. J. Immunolocalization of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues. Lab Invest. 1991 Mar;64(3):313–320. [PubMed] [Google Scholar]
  18. Lazarevic M. B., Yan K., Swedler W. I., Rasenick M. M., Skosey J. L. Effect of gold compounds on the activity of adenylyl cyclase in human lymphocyte membranes. Arthritis Rheum. 1992 Aug;35(8):857–864. doi: 10.1002/art.1780350803. [DOI] [PubMed] [Google Scholar]
  19. Leeuwenberg J. F., von Asmuth E. J., Jeunhomme T. M., Buurman W. A. IFN-gamma regulates the expression of the adhesion molecule ELAM-1 and IL-6 production by human endothelial cells in vitro. J Immunol. 1990 Oct 1;145(7):2110–2114. [PubMed] [Google Scholar]
  20. Maciag T., Cerundolo J., Ilsley S., Kelley P. R., Forand R. An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5674–5678. doi: 10.1073/pnas.76.11.5674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marks D. C., Belov L., Davey M. W., Davey R. A., Kidman A. D. The MTT cell viability assay for cytotoxicity testing in multidrug-resistant human leukemic cells. Leuk Res. 1992 Dec;16(12):1165–1173. doi: 10.1016/0145-2126(92)90114-m. [DOI] [PubMed] [Google Scholar]
  22. Matsubara T., Ziff M. Inhibition of human endothelial cell proliferation by gold compounds. J Clin Invest. 1987 May;79(5):1440–1446. doi: 10.1172/JCI112972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morales-Ducret J., Wayner E., Elices M. J., Alvaro-Gracia J. M., Zvaifler N. J., Firestein G. S. Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol. 1992 Aug 15;149(4):1424–1431. [PubMed] [Google Scholar]
  24. Munro J. M., Pober J. S., Cotran R. S. Tumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. Am J Pathol. 1989 Jul;135(1):121–133. [PMC free article] [PubMed] [Google Scholar]
  25. Munthe E., Jellum E. Is gold necessary in so called chrysotherapy? Scand J Rheumatol Suppl. 1983;51:46–51. doi: 10.3109/03009748309095343. [DOI] [PubMed] [Google Scholar]
  26. Pober J. S., Slowik M. R., De Luca L. G., Ritchie A. J. Elevated cyclic AMP inhibits endothelial cell synthesis and expression of TNF-induced endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1. J Immunol. 1993 Jun 1;150(11):5114–5123. [PubMed] [Google Scholar]
  27. Rohde D., Schlüter-Wigger W., Mielke V., von den Driesch P., von Gaudecker B., Sterry W. Infiltration of both T cells and neutrophils in the skin is accompanied by the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1): an immunohistochemical and ultrastructural study. J Invest Dermatol. 1992 May;98(5):794–799. doi: 10.1111/1523-1747.ep12499959. [DOI] [PubMed] [Google Scholar]
  28. Rudge S. R., Perrett D., Kelly M. Failure of oral thiomalate to act as an alternative to intramuscular gold in rheumatoid arthritis. Ann Rheum Dis. 1988 Mar;47(3):224–227. doi: 10.1136/ard.47.3.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rudge S. R., Perrett D., Swannell A. J., Drury P. L. Circulating thiomalate after administration of disodium aurothiomalate: impurity or active metabolite? J Rheumatol. 1984 Apr;11(2):150–152. [PubMed] [Google Scholar]
  30. Scheinberg M. A., Santos L. M., Finkelstein A. E. The effect of auranofin and sodium aurothiomalate on peripheral blood monocytes. J Rheumatol. 1982 May-Jun;9(3):366–369. [PubMed] [Google Scholar]
  31. Veale D., Yanni G., Rogers S., Barnes L., Bresnihan B., Fitzgerald O. Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis. Arthritis Rheum. 1993 Jul;36(7):893–900. doi: 10.1002/art.1780360705. [DOI] [PubMed] [Google Scholar]
  32. Wellicome S. M., Thornhill M. H., Pitzalis C., Thomas D. S., Lanchbury J. S., Panayi G. S., Haskard D. O. A monoclonal antibody that detects a novel antigen on endothelial cells that is induced by tumor necrosis factor, IL-1, or lipopolysaccharide. J Immunol. 1990 Apr 1;144(7):2558–2565. [PubMed] [Google Scholar]
  33. Yocum D. E., Esparza L., Dubry S., Benjamin J. B., Volz R., Scuderi P. Characteristics of tumor necrosis factor production in rheumatoid arthritis. Cell Immunol. 1989 Aug;122(1):131–145. doi: 10.1016/0008-8749(89)90154-8. [DOI] [PubMed] [Google Scholar]

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

RESOURCES