Elsevier

Life Sciences

Volume 60, Issue 17, 21 March 1997, Pages 1487-1496
Life Sciences

Cyclosporin-A inhibits human endothelial cells proliferation through interleukin-6-dependent mechanisms

https://doi.org/10.1016/S0024-3205(97)00100-8Get rights and content

Abstract

Cyclosporine A (CsA) is a widely used immunosuppressant which possesses significant side effects including nephrotoxicity and systemic arterial hypertension. In this work we evaluated the effects of CsA on human umbilical endothelial cell proliferation (HUVEC). Treatment of endothelial cells with CsA inhibited cell proliferation, and was correlated with an increase of interleukin-6 (IL-6) production and IL-6 mRNA expression. Addition of exogenous IL-6 also significantly altered cell proliferation. Furthermore, neutralization of endogenous IL-6 with a specific monoclonal antibody concomitantly with CsA treatment completly restored HUVEC proliferation. These results suggest that CsA-induced inhibition of HUVEC proliferation is mediated through an augmentation of IL-6 synthesis.

References (47)

  • J. Liu et al.

    Cell

    (1991)
  • M.J.W. Zaal et al.

    Lancet

    (1988)
  • L. Osborn

    Cell

    (1990)
  • C. Delomenie et al.

    Exp. Cell Res.

    (1993)
  • L.T. May et al.

    Biochem. Biophys. Res. Commun.

    (1989)
  • E. Borenfreund et al.

    Toxicol. Lett.

    (1985)
  • M. Bouaboula et al.

    J. Biol. Chem.

    (1992)
  • M.R. Shalaby et al.

    Cell. Immunol.

    (1989)
  • J.E. Tanner et al.

    Blood

    (1994)
  • J. Sanceau et al.

    J. Biol. Chem.

    (1995)
  • S.F. Yan et al.

    J. Biol. Chem.

    (1995)
  • E.A. Emmel et al.

    Science

    (1989)
  • C. Randak et al.

    EMBO J.

    (1990)
  • M.T. Olivari et al.

    J. Heart Transplant.

    (1989)
  • B.D. Myers et al.

    N. Engl. J. Med.

    (1984)
  • B.S. Edwards et al.

    Transplantation

    (1993)
  • J. English et al.

    Transplantation

    (1987)
  • T.P. Loughran et al.

    Br. J. Haematol.

    (1985)
  • J.J. Curtis et al.

    Am. J. Med.

    (1988)
  • U. Scherrer et al.

    N. Engl. J. Med.

    (1990)
  • J. Mason

    Pharmacol. Rev.

    (1989)
  • B.L. Voss et al.

    Transplantation

    (1988)
  • Z. Brown et al.

    Biochem. Pharmacol.

    (1990)
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