Molecular and Cellular Biochemistry

, Volume 177, Issue 1–2, pp 177–181 | Cite as

Pyrrolidine dithiocarbamate inhibits cytokine-induced VCAM-1 gene expression in rat cardiac myocytes

  • Yoshiyuki Hattori
  • Kazumi Akimoto
  • Yasuyuki Murakami
  • Kikuo Kasai

Abstract

We investigated whether interleukin-1α (IL-1) would induce gene expression of vascular cell adhesion molecule-1 (VCAM-1) in cardiac myocytes and, if so, whether nuclear factor κB (NF-κB) was involved. We evaluated the VCAM-1 gene expression in cultured neonatal rat cardiac myocytes by the reverse transcription-polymerase chain reaction. IL-1 alone or together with interferon-γ (IFN) induced VCAM-1 gene expression in the cells. Induction of VCAM-1 gene expression in response to IL-1 and IFN was antagonized in a concentration-dependent manner by pyrrolidine dithiocarbamate, an inhibitor of NF-κb activation (25-100 µM). Tosyl-lysine-chloromethyl ketone, another inhibitor of NF-κb activation, also inhibited the expression of the VCAM-1 gene in response to IL-1 and IFN. Thus, VCAM-1 gene expression appeared to be mediated by NF-κb in cardiac myocytes, and this cardiac myocyte VCAM-1 may be involved in cardiac inflammatory disorders. Disruption of expression of VCAM-1 by inhibition of NF-κb activation may indicate a target for pharmacologic intervention intended to limit cardiac inflammation.

vascular cell adhesion molecule 1 (VCAM-1) nuclear factor κB (NF-κB) interleukin-1α (IL-1) cardiac myocyte 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Korthuis RJ, Anderson DC, Granger DN: Role of neutrophil-endothelial cell adhesion in inflammatory disorders. J Crit Care 9: 47–71, 1994Google Scholar
  2. 2.
    Kukielka GL, Hawkins HK, Michael L, Manning AM, Youker K, Lane C, Entman ML, Smith CW, Anderson DC: Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium. J Clin Invest 92: 1504–1516, 1993Google Scholar
  3. 3.
    Kurose I, Anderson DC, Miyasaka M, Tamatani T, Paulson RF, Todd RF, Rusche JR, Granger DN: Molecular determinants of reperfusion-induced leukocyte adhesion and vascular protein leakage. Circ Res 74: 336–343, 1994Google Scholar
  4. 4.
    Ioculano M, Squadrito F, Altavilla D, Canale P, Squadrito G, Campo GM, Saitta A, Caputi AP: Antibodies against intercellular adhesion molecule 1 protect against myocardial ischaemia-reperfusion injury in rat. Eur J Pharmacol 264: 143–149, 1994Google Scholar
  5. 5.
    Xu H, Gonzzalo JA, Pierre YS, Williams IR, Kupper TS, Cotran RS, Springer TA, Gutierrez RJ: Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J Exp Med 180: 95–109, 1994Google Scholar
  6. 6.
    Tanaka H, Sukhova GK, Swanson SJ, Cybulsky MI, Schoen FJ, Libby P: Endothelial and smooth muscle cells express leukocyte adhesion molecules heterogeneously during acute rejection of rabbit cardiac allografts. Am J Pathol 44: 938–951, 1994Google Scholar
  7. 7.
    Ardehali A, Laks H, Drinkwater DC, Ziv E, Drake TA: Vascular cell adhesion molecule-1 is induced on vascular endothelia and medial smooth muscle cells in experimental cardiac allograft vasculopathy. Circulation 92: 450–456, 1995Google Scholar
  8. 8.
    Schowengerdt KO, Zhu JY, Stepkowski SM, Tu Y, Entman ML, Ballantyne CM: Cardiac allograft survival in mice deficient in intercellular adhesion molecule-1. Circulation 92: 82–87, 1995Google Scholar
  9. 9.
    Deng MC, Bell S, Huie P, Pinto F, Hunt SA, Stinson EB, Sibley R, Hall BM, Valantine HA: Cardiac allograft vascular disease. Relationship to microvascular cell surface markers and inflammatory cell phenotypes on endomyocardial biopsy. Circulation 91: 1647–1654, 1995Google Scholar
  10. 10.
    Iademarco MF, McQuillan JJ, Rosen GD, Dean DC: Characterization of the promoter for vascular cell adhesion molecule 1. J Biol Chem 267: 16323–16329, 1992Google Scholar
  11. 11.
    Neish AS, Williams AJ, Palmer HJ, Whitley MZ, Collins T: Functional analysis of the vascular cell adhesion molecule 1 promoter. J Exp Med 176: 1583–1593, 1992Google Scholar
  12. 12.
    Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA: Dithiocarbamates as potent inhibitors of nuclear factor kB activation in intact cells. J Exp Med 175: 1181–1194, 1992Google Scholar
  13. 13.
    Hattori Y, Nakanishi N, Kasai K, Shimoda S, Gross SS: Pyrrolidine dithiocarbamate inhibits immunostimulant-induced tetrahydrobiopterin synthesis in rat vascular smooth muscle. Eur J Pharmacol 296: 107–112, 1996Google Scholar
  14. 14.
    Kamitani T, Ikeda U, Muto S, Kawakami K, Nagano K, Tsuruya Y, Oguchi A, Yamamoto K, Hara Y, Kojima T, Medford RM, Shimada K: Regulation of Na, K-ATPase gene expression by thyroid hormone in rat cardiocytes. Circ Res 71: 1457–1464, 1992Google Scholar
  15. 15.
    Hattori Y, So S, Hattori S, Kasai K, Shimoda S: Vesnarinone inhibits induction of nitric oxide synthase in J774 macrophages and rat cardiac myocytes in culture. Cardiovasc Res 30: 187–192, 1995Google Scholar
  16. 16.
    Ham RG: Clonal growth of diploid Chinese hamster cells in a synthetic medium supplemented with purified protein fractions. Exp Cell Res 28: 489–500, 1962Google Scholar
  17. 17.
    Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159, 1987Google Scholar
  18. 18.
    Hattori Y, Gross SS: GTP cyclohydrolase I mRNA is induced by LPS in vascular smooth muscle: Characterization, sequence and relationship to nitric oxide synthase. Biochem Biophys Res Commun 195: 435–441, 1993Google Scholar
  19. 19.
    Terada Y, Tomita K, Nonoguchi H, Marumo F: Polymerase chain reaction localization of constitutive nitric oxide synthase and soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments. J Clin Invest 90: 659–665, 1992Google Scholar
  20. 20.
    Hattori Y, Oka M, Kasai K, Nakanishi N, Shimoda S: Lipopoly-saccharide treatment in vivo induces tissue expression of GTP cyclohydrolase I mRNA. FEBS Lett 368: 336–338, 1995Google Scholar
  21. 21.
    Hession C, Moy P, Tizard R, Chisholm P, Williams C, Wysk M, Burkly L, Miyake K, Kincade P, Lobb R: Cloning of murine and rat vascular cell adhesion molecule-1. Biochem Biophys Res Commun 183: 163–169, 1992Google Scholar
  22. 22.
    Fries JWU, Williams AJ, Atkins RC, Newman W, Lipscomb MF, Collins T: Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation. Am J Pathol 143: 725–737, 1993Google Scholar
  23. 23.
    Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 655: 55–63, 1983Google Scholar
  24. 24.
    Barry WH: Mechanisms of immune-mediated myocyte injury. Circulation 89: 2421–2432, 1994Google Scholar
  25. 25.
    Lange LG, Schreiner GF: Immune mechanisms of cardiac disease. N Engl J Med 174: 493–496, 1994Google Scholar
  26. 26.
    Oddis CV, Finkel MS: NF-kB and GTP cyclohydrolase regulate cytokine-induced nitric oxide production by cardiac myocytes. Am J Physiol 270: H1864–H1868, 1996Google Scholar
  27. 27.
    Chen CC, Rosenbloom CL, Anderson DC, Manning AM: Selective inhibition of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 expression by inhibitors of IkB-αphosphorylation. J Immunol 155: 3538–3545, 1995Google Scholar
  28. 28.
    Griscavage JM, Wilk S, Ignarro LJ: Serine and cysteine proteinase inhibitors prevent nitric oxide production by activated macrophages by interfering with transcription of the inducible NO synthase gene. Biochem Biophys Res Commun 13: 721–729, 1995Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Yoshiyuki Hattori
    • 1
  • Kazumi Akimoto
    • 2
  • Yasuyuki Murakami
    • 1
  • Kikuo Kasai
    • 1
  1. 1.Department of EndocrinologyDokkyo University School of MedicineJapan
  2. 2.Laboratory of Molecular and Cellular BiologyDokkyo University School of MedicineJapan

Personalised recommendations